Platelets: Novel Biomaterials for Cancer Diagnosis and Therapeutic Delivery

Abstract

Platelets play a pivotal role in cancer detection and metastasis, serving both as novel liquid biopsy biomarkers and as versatile carriers in nanomedicine. Tumor-educated platelets (TEPs) undergo molecular alterations influenced by the tumor microenvironment, with their RNA profiles—including mRNA, circular RNA, and long noncoding RNA—offering potential for early cancer detection, prognosis, and treatment monitoring. Additionally, platelet-derived extracellular vesicles (PEVs) and activation markers (e.g., P-selectin, CD40L) further enhance their diagnostic utility. However, standardization of platelet biomarker analysis remains a challenge for clinical implementation. Concurrently, nanotechnology is leveraging the natural biocompatibility and targeting properties of platelets to develop platelet-based drug delivery systems and bioinspired nanomaterials, improving therapeutic precision and efficacy. Moreover, artificial intelligence (AI)-driven biomarker analysis is refining TEP and PEV profiling, accelerating advances in precision oncology. Future research should focus on establishing standardized protocols, optimizing platelet-based nanomedicine, and integrating AI to enhance diagnostic accuracy and therapeutic efficacy. By bridging biological insights with clinical applications, platelets hold significant promise as transformative tools in precision oncology.

Keywords

circulating tumor cells / diagnose / platelet-based nanomaterials / platelets / tumor-educated platelets

References

[1] R. L. Siegel, K. D. Miller, N. S. Wagle, and A. Jemal, “Cancer Statistics, 2023,” CA: A Cancer Journal for Clinicians 73 (2023): 17–48.

[2] L. Rahib, B. D. Smith, R. Aizenberg, A. B. Rosenzweig, J. M. Fleshman, and L. M. Matrisian, “Projecting Cancer Incidence and Deaths to 2030: The Unexpected Burden of Thyroid, Liver, and Pancreas Cancers in the United States,” Cancer Research 74 (2014): 2913–2921.

[3] L. B. Alexandrov, S. Nik-Zainal, D. C. Wedge, et al., “Signatures of Mutational Processes in Human Cancer,” Nature 500 (2013): 415–421.

[4] R. Barouch-Bentov and K. Sauer, “Mechanisms of Drug Resistance in Kinases,” Expert Opinion on Investigational Drugs 20 (2011): 153–208.

[5] C. Holohan, S. Van Schaeybroeck, D. B. Longley, and P. G. Johnston, “Cancer Drug Resistance: An Evolving Paradigm,” Nature Reviews Cancer 13 (2013): 714–726.

[6] J. Wu, S. Hu, L. Zhang, et al., “Tumor Circulome in the Liquid Biopsies for Cancer Diagnosis and Prognosis,” Theranostics 10 (2020): 4544–4556.

[7] P. Economopoulou, I. Kotsantis, E. Kyrodimos, E. S. Lianidou, and A. Psyrri, “Liquid Biopsy: An Emerging Prognostic and Predictive Tool in Head and Neck Squamous Cell Carcinoma (HNSCC). Focus on Circulating Tumor Cells (CTCs),” Oral Oncology 74 (2017): 83–89.

[8] K. Pantel and C. Alix-Panabières, “Circulating Tumour Cells in Cancer Patients: Challenges and Perspectives,” Trends in Molecular Medicine 16 (2010): 398–406.

[9] L. Zhang, L. D. Ridgway, M. D. Wetzel, et al., “The Identification and Characterization of Breast Cancer CTCs Competent for Brain Metastasis,” Science Translational Medicine 5 (2013): 180ra48.

[10] L. Console, M. Scalise, and C. Indiveri, “Exosomes in Inflammation and Role as Biomarkers,” Clinica Chimica Acta 488 (2019): 165–171.

[11] Y. Shao, Y. Shen, T. Chen, F. Xu, X. Chen, and S. Zheng, “The Functions and Clinical Applications of Tumor-Derived Exosomes,” Oncotarget 7 (2016): 60736–60751.

[12] S. A. Joosse and K. Pantel, “Tumor-Educated Platelets as Liquid Biopsy in Cancer Patients,” Cancer Cell 28 (2015): 552–554.

[13] S. Asghar, W. Waqar, M. Umar, and S. Manzoor, “Tumor Educated Platelets, a Promising Source for Early Detection of Hepatocellular Carcinoma: Liquid Biopsy an Alternative Approach to Tissue Biopsy,” Clinics and Research in Hepatology and Gastroenterology 44 (2020): 836–844.

[14] L. Liu, F. Lin, X. Ma, Z. Chen, and J. Yu, “Tumor-Educated Platelet as Liquid Biopsy in Lung Cancer Patients,” Critical Reviews in Oncology/Hematology 146 (2020): 102863.

[15] S. G. J. G. In ‘t Veld, M. Arkani, E. Post, et al., “Detection and Localization of Early- and Late-Stage Cancers Using Platelet RNA,” Cancer Cell 40 (2022): 999–1009.e6.

[16] K. R. Machlus, J. N. Thon, and J. E. Italiano, , “Interpreting the Developmental Dance of the Megakaryocyte: A Review of the Cellular and Molecular Processes Mediating Platelet Formation,” British Journal of Haematology 165 (2014): 227–236.

[17] L. A. Harker, L. K. Roskos, U. M. Marzec, et al., “Effects of Megakaryocyte Growth and Development Factor on Platelet Production, Platelet Life Span, and Platelet Function in Healthy Human Volunteers,” Blood 95 (2000): 2514–2522.

[18] I. D. Pokrovskaya, S. Yadav, A. Rao, et al., “3D Ultrastructural Analysis of α-Ggranule, Dense Granule, Mitochondria, and Canalicular System Arrangement in Resting Human Platelets,” Research and Practice in Thrombosis and Haemostasis 4 (2020): 72–85.

[19] A. Grichine, S. Jacob, A. Eckly, et al., “The Fate of Mitochondria During Platelet Activation,” Blood Advances 7 (2023): 6290–6302.

[20] Y. Ding, X. Gui, X. Chu, et al., “MTH1 Protects Platelet Mitochondria From Oxidative Damage and Regulates Platelet Function and Thrombosis,” Nature Communications 14 (2023): 4829.

[21] A. L. Palacios-Acedo, D. Mège, L. Crescence, F. Dignat-George, C. Dubois, and L. Panicot-Dubois, “Platelets, Thrombo-Inflammation, and Cancer: Collaborating With the Enemy,” Frontiers in Immunology 10 (2019): 1805.

[22] N. M. Bambace and C. E. Holmes, “The Platelet Contribution to Cancer Progression,” Journal of Thrombosis and Haemostasis 9 (2011): 237–249.

[23] S. Anvari, E. Osei, and N. Maftoon, “Interactions of Platelets With Circulating Tumor Cells Contribute to Cancer Metastasis,” Scientific Reports 11 (2021): 15477.

[24] M. Labelle, S. Begum, and R. O. Hynes, “Direct Signaling Between Platelets and Cancer Cells Induces an Epithelial-Mesenchymal-Like Transition and Promotes Metastasis,” Cancer Cell 20 (2011): 576–590.

[25] E. Marcolino, Y. H. Siddiqui, M. van den Bosch, A. W. Poole, P. S. Jayaraman, and K. Gaston, “Blood Platelets Stimulate Cancer Extravasation Through TGFβ-mediated Downregulation of PRH/HHEX,” Oncogenesis 9 (2020): 10.

[26] L. Zhou, Z. Zhang, Y. Tian, Z. Li, Z. Liu, and S. Zhu, “The Critical Role of Platelet in Cancer Progression and Metastasis,” European Journal of Medical Research 28 (2023): 385.

[27] J. Ren, J. He, H. Zhang, et al., “Platelet TLR4-ERK5 Axis Facilitates NET-Mediated Capturing of Circulating Tumor Cells and Distant Metastasis After Surgical Stress,” Cancer Research 81 (2021): 2373–2385.

[28] S. Sabrkhany, M. J. E. Kuijpers, M. G. A. Oude Egbrink, and A. W. Griffioen, “Platelets as Messengers of Early-Stage Cancer,” Cancer and Metastasis Reviews 40 (2021): 563–573.

[29] R. Gu, X. Sun, Y. Chi, et al., “Integrin β3/Akt Signaling Contributes to Platelet-Induced Hemangioendothelioma Growth,” Scientific Reports 7 (2017): 6455.

[30] K. Suzuki-Inoue, “A Novel Syk-Dependent Mechanism of Platelet Activation by the C-Type Lectin Receptor CLEC-2,” Blood 107 (2006): 542–549.

[31] V. O. Melnikova, A. A. Mourad-Zeidan, D. C. Lev, and M. Bar-Eli, “Platelet-Activating Factor Mediates MMP-2 Expression and Activation via Phosphorylation of cAMP-Response Element-Binding Protein and Contributes to Melanoma Metastasis,” Journal of Biological Chemistry 281 (2006): 2911–2922.

[32] M. M. Denis, N. D. Tolley, M. Bunting, et al., “Escaping the Nuclear Confines: Signal-Dependent Pre-mRNA Splicing in Anucleate Platelets,” Cell 122 (2005): 379–391.

[33] M. P. Ward, L. E. Kane, L. A. Norris, et al., “Platelets, Immune Cells and the Coagulation Cascade; Friend or Foe of the Circulating Tumour Cell?,” Molecular Cancer 20 (2021): 59.

[34] S. A. Joosse, T. M. Gorges, and K. Pantel, “Biology, Detection, and Clinical Implications of Circulating Tumor Cells,” EMBO Molecular Medicine 7 (2015): 1–11.

[35] S. Meng, D. Tripathy, E. P. Frenkel, et al., “Circulating Tumor Cells in Patients With Breast Cancer Dormancy,” Clinical Cancer Research 10 (2004): 8152–8162.

[36] V. K. Chivukula, B. L. Krog, J. T. Nauseef, M. D. Henry, and S. C. Vigmostad, “Alterations in Cancer Cell Mechanical Properties After Fluid Shear Stress Exposure: A Micropipette Aspiration Study,” Cell Health and Cytoskeleton 7 (2015): 25–35.

[37] B. A. Kerr, N. P. McCabe, W. Feng, and T. V. Byzova, “Platelets Govern Pre-Metastatic Tumor Communication to Bone,” Oncogene 32 (2013): 4319–4324.

[38] A. Rodriguez-Martinez, I. Simon-Saez, S. Perales, et al., “Exchange of Cellular Components Between Platelets and Tumor Cells: Impact on Tumor Cells Behavior,” Theranostics 12 (2022): 2150–2161.

[39] T. Dudiki, M. Veleeparambil, I. Zhevlakova, et al., “Mechanism of Tumor-Platelet Communications in Cancer,” Circulation Research 132 (2023): 1447–1461.

[40] M. E. Quach and R. Li, “Structure-Function of Platelet Glycoprotein Ib-IX,” Journal of Thrombosis and Haemostasis 18 (2020): 3131–3141.

[41] L. Plantureux, D. Mège, L. Crescence, F. Dignat-George, C. Dubois, and L. Panicot-Dubois, “Impacts of Cancer on Platelet Production, Activation and Education and Mechanisms of Cancer-Associated Thrombosis,” Cancers 10 (2018): 441.

[42] N. Abdol Razak, G. Jones, M. Bhandari, M. Berndt, and P. Metharom, “Cancer-Associated Thrombosis: An Overview of Mechanisms, Risk Factors, and Treatment,” Cancers 10 (2018): 380.

[43] P. G. Cavanaugh, B. F. Sloane, and K. V. Honn, “Role of the Coagulation System in Tumor-Cell-Induced Platelet Aggregation and Metastasis,” Haemostasis 18 (1988): 37–46.

[44] K. Suzuki-Inoue, “Roles of the CLEC-2-Podoplanin Interaction in Tumor Progression,” Platelets 29 (2018): 786–792.

[45] K. Suzuki-Inoue, “Platelets and Cancer-Associated Thrombosis: Focusing on the Platelet Activation Receptor CLEC-2 and Podoplanin,” Blood 134 (2019): 1912–1918.

[46] C. Ma, Q. Fu, L. P. Diggs, et al., “Platelets Control Liver Tumor Growth Through P2Y12-Dependent CD40L Release in NAFLD,” Cancer Cell 40 (2022): 986–998.

[47] L. X. Yu, L. Yan, W. Yang, et al., “Platelets Promote Tumour Metastasis via Interaction Between TLR4 and Tumour Cell-Released High-Mobility Group Box 1 Protein,” Nature Communications 5 (2014): 5256.

[48] B. Estevez and X. Du, “New Concepts and Mechanisms of Platelet Activation Signaling,” Physiology 32 (2017): 162–177.

[49] G. Xiong, J. Chen, G. Zhang, et al., “Hsp47 Promotes Cancer Metastasis by Enhancing Collagen-Dependent Cancer Cell-Platelet Interaction,” Proceedings of the National Academy of Sciences 117 (2020): 3748–3758.

[50] H. Krishnan, J. Rayes, T. Miyashita, et al., “Podoplanin: An Emerging Cancer Biomarker and Therapeutic Target,” Cancer Science 109 (2018): 1292–1299.

[51] J. Riedl, M. Preusser, P. M. S. Nazari, et al., “Podoplanin Expression in Primary Brain Tumors Induces Platelet Aggregation and Increases Risk of Venous Thromboembolism,” Blood 129 (2017): 1831–1839.

[52] J. Rayes, S. P. Watson, and B. Nieswandt, “Functional Significance of the Platelet Immune Receptors GPVI and CLEC-2,” Journal of Clinical Investigation 129 (2019): 12–23.

[53] E. Mammadova-Bach, J. Gil-Pulido, E. Sarukhanyan, et al., “Platelet Glycoprotein VI Promotes Metastasis Through Interaction With Cancer Cell-Derived Galectin-3,” Blood 135 (2020): 1146–1160.

[54] B. Saha, T. Mathur, J. J. Tronolone, et al., “Human Tumor Microenvironment Chip Evaluates the Consequences of Platelet Extravasation and Combinatorial Antitumor-Antiplatelet Therapy in Ovarian Cancer,” Science Advances 7 (2021): eabg5283.

[55] J. Ichikawa, T. Ando, T. Kawasaki, et al., “Role of Platelet C-Type Lectin-Like Receptor 2 in Promoting Lung Metastasis in Osteosarcoma,” Journal of Bone and Mineral Research 35 (2020): 1738–1750.

[56] A. Mitrugno, D. Williams, S. W. Kerrigan, and N. Moran, “A Novel and Essential Role for FcγRIIa in Cancer Cell-Induced Platelet Activation,” Blood 123 (2014): 249–260.

[57] Y. Ward, R. Lake, F. Faraji, et al., “Platelets Promote Metastasis via Binding Tumor CD97 Leading to Bidirectional Signaling That Coordinates Transendothelial Migration,” Cell Reports 23 (2018): 808–822.

[58] X. Zuo, Y. Yang, Y. Zhang, Z. Zhang, X. Wang, and Y. Shi, “Platelets Promote Breast Cancer Cell MCF-7 Metastasis by Direct Interaction: Surface Integrin α2β1-Contacting-Mediated Activation of Wnt-β-Catenin Pathway,” Cell Communication and Signaling 17 (2019): 142.

[59] P. Pai and S. Sukumar, “Hox Genes and the NF-κB Pathway: A Convergence of Developmental Biology, Inflammation and Cancer Biology,” Biochimica et Biophysica Acta (BBA)—Reviews on Cancer 1874 (2020): 188450.

[60] R. Leblanc and O. Peyruchaud, “Metastasis: New Functional Implications of Platelets and Megakaryocytes,” Blood 128 (2016): 24–31.

[61] S. Pan, Y. Hu, M. Hu, et al., “Platelet-Derived PDGF Promotes the Invasion and Metastasis of Cholangiocarcinoma by Upregulating MMP2/MMP9 Expression and Inducing EMT via the p38/MAPK Signalling Pathway,” American Journal of Translational Research 12 (2020): 3577–3595.

[62] A. Metelli, B. X. Wu, B. Riesenberg, et al., “Thrombin Contributes to Cancer Immune Evasion via Proteolysis of Platelet-Bound GARP to Activate LTGF-β,” Science Translational Medicine 12 (2020): eaay4860.

[63] A. T. Bauer, J. Suckau, K. Frank, et al., “Von Willebrand Factor Fibers Promote Cancer-Associated Platelet Aggregation in Malignant Melanoma of Mice and Humans,” Blood 125 (2015): 3153–3163.

[64] S. Jain, M. Zuka, J. Liu, et al., “Platelet Glycoprotein Ibα Supports Experimental Lung Metastasis,” Proceedings of the National Academy of Sciences 104 (2007): 9024–9028.

[65] X. Liu, J. Song, H. Zhang, et al., “Immune Checkpoint HLA-E:CD94-NKG2A Mediates Evasion of Circulating Tumor Cells From NK Cell Surveillance,” Cancer Cell 41 (2023): 272–287.e9.

[66] J. E. Geddings, Y. Hisada, Y. Boulaftali, et al., “Tissue Factor-Positive Tumor Microvesicles Activate Platelets and Enhance Thrombosis in Mice,” Journal of Thrombosis and Haemostasis 14 (2016): 153–166.

[67] B. Shao, M. G. Wahrenbrock, L. Yao, et al., “Carcinoma Mucins Trigger Reciprocal Activation of Platelets and Neutrophils in a Murine Model of Trousseau Syndrome,” Blood 118 (2011): 4015–4023.

[68] J. Cedervall, A. Hamidi, and A. K. Olsson, “Platelets, NETs and Cancer,” Thrombosis Research 164, no. Suppl 1 (2018): S148–S152.

[69] M. Yan and P. Jurasz, “The Role of Platelets in the Tumor Microenvironment: From Solid Tumors to Leukemia,” Biochimica et Biophysica Acta (BBA)—Molecular Cell Research 1863 (2016): 392–400.

[70] M. S. Cho, J. Bottsford-Miller, H. G. Vasquez, et al., “Platelets Increase the Proliferation of Ovarian Cancer Cells,” Blood 120 (2012): 4869–4872.

[71] A. Radziwon-Balicka, C. Medina, L. O'Driscoll, et al., “Platelets Increase Survival of Adenocarcinoma Cells Challenged With Anticancer Drugs: Mechanisms and Implications for Chemoresistance,” British Journal of Pharmacology 167 (2012): 787–804.

[72] M. Labelle, S. Begum, and R. O. Hynes, “Platelets Guide the Formation of Early Metastatic Niches,” Proceedings of the National Academy of Sciences 111 (2014): E3053–E3061.

[73] R. Romero-Moreno, K. J. Curtis, T. R. Coughlin, et al., “The CXCL5/CXCR2 Axis Is Sufficient to Promote Breast Cancer Colonization During Bone Metastasis,” Nature Communications 10 (2019): 4404.

[74] N. Aceto, A. Bardia, D. T. Miyamoto, et al., “Circulating Tumor Cell Clusters Are Oligoclonal Precursors of Breast Cancer Metastasis,” Cell 158 (2014): 1110–1122.

[75] S. Gkountela, F. Castro-Giner, B. M. Szczerba, et al., “Circulating Tumor Cell Clustering Shapes DNA Methylation to Enable Metastasis Seeding,” Cell 176 (2019): 98–112.e14.

[76] H. Chopra, J. Timar, X. Rong, et al., “Is There a Role for the Tumor Cell Integrin alpha IIb beta 3 and Cytoskeleton in Tumor Cell-Platelet Interaction?,” Clinical & Experimental Metastasis 10 (1992): 125–137.

[77] R. Leblanc, S. C. Lee, M. David, et al., “Interaction of Platelet-Derived Autotaxin With Tumor Integrin αVβ3 Controls Metastasis of Breast Cancer Cells to Bone,” Blood 124 (2014): 3141–3150.

[78] M. Yan, G. Lesyk, A. Radziwon-Balicka, and P. Jurasz, “Pharmacological Regulation of Platelet Factors That Influence Tumor Angiogenesis,” Seminars in Oncology 41 (2014): 370–377.

[79] A. Radziwon-Balicka, C. Moncada de la Rosa, and P. Jurasz, “Platelet-Associated Angiogenesis Regulating Factors: A Pharmacological Perspective,” Canadian Journal of Physiology and Pharmacology 90 (2012): 679–688.

[80] E. Ricciotti and G. A. FitzGerald, “Aspirin in the Prevention of Cardiovascular Disease and Cancer,” Annual Review of Medicine 72 (2021): 473–495.

[81] H. F. G. Heijnen, A. E. Schiel, R. Fijnheer, H. J. Geuze, and J. J. Sixma, “Activated Platelets Release Two Types of Membrane Vesicles: Microvesicles by Surface Shedding and Exosomes Derived From Exocytosis of Multivesicular Bodies and α-Granules,” Blood 94 (1999): 3791–3799.

[82] F. Li, T. Xu, P. Chen, et al., “Platelet-Derived Extracellular Vesicles Inhibit Ferroptosis and Promote Distant Metastasis of Nasopharyngeal Carcinoma by Upregulating ITGB3,” International Journal of Biological Sciences 18 (2022): 5858–5872.

[83] S. Lazar and L. E. Goldfinger, “Platelets and Extracellular Vesicles and Their Cross Talk With Cancer,” Blood 137 (2021): 3192–3200.

[84] D. Cacic, H. Reikvam, O. Nordgård, P. Meyer, and T. Hervig, “Platelet Microparticles Protect Acute Myelogenous Leukemia Cells against Daunorubicin-Induced Apoptosis,” Cancers 13 (2021): 1870.

[85] S. E. Bailey, O. C. Ukoumunne, E. A. Shephard, and W. Hamilton, “Clinical Relevance of Thrombocytosis in Primary Care: A Prospective Cohort Study of Cancer Incidence Using English Electronic Medical Records and Cancer Registry Data,” British Journal of General Practice 67 (2017): e405–e413.

[86] G. O. Abdulrahman, N. Das, and K. Lutchman Singh, “The Predictive Role of Thrombocytosis in Benign, Borderline and Malignant Ovarian Tumors,” Platelets 31 (2020): 795–800.

[87] S. G. Hwang, K. M. Kim, J. H. Cheong, et al., “Impact of Pretreatment Thrombocytosis on Blood-Borne Metastasis and Prognosis of Gastric Cancer,” European Journal of Surgical Oncology (EJSO) 38 (2012): 562–567.

[88] P. Skorek, K. Stępień, M. Fila, et al, “Preoperative Thrombocytosis in Surgically Treated Patients With Non-Small Cell Lung Cancer,” Polish Archives of Internal Medicine 128 (2018): 512–517.

[89] R. L. Stone, A. M. Nick, I. A. McNeish, et al., “Paraneoplastic Thrombocytosis in Ovarian Cancer,” New England Journal of Medicine 366 (2012): 610–618.

[90] K. Harano, T. Kogawa, J. Wu, et al., “Thrombocytosis as a Prognostic Factor in Inflammatory Breast Cancer,” Breast Cancer Research and Treatment 166 (2017): 819–832.

[91] F. Pucci, S. Rickelt, A. P. Newton, et al., “PF4 Promotes Platelet Production and Lung Cancer Growth,” Cell Reports 17 (2016): 1764–1772.

[92] A. Suzuki, T. Takahashi, K. Nakamura, et al., “Thrombocytosis in Patients With Tumors Producing Colony-Stimulating Factor,” Blood 80 (1992): 2052–2059.

[93] H. G. Roweth, M. W. Malloy, G. J. Goreczny, et al., “Pro-Inflammatory Megakaryocyte Gene Expression in Murine Models of Breast Cancer,” Science Advances 8 (2022): eabo5224.

[94] P. Detopoulou, G. I. Panoutsopoulos, M. Mantoglou, et al., “Relation of Mean Platelet Volume (MPV) With Cancer: A Systematic Review With a Focus on Disease Outcome on Twelve Types of Cancer,” Current Oncology 30 (2023): 3391–3420.

[95] K. Pogorzelska, A. Krętowska, M. Krawczuk-Rybak, and M. Sawicka-Żukowska, “Characteristics of Platelet Indices and Their Prognostic Significance in Selected Medical Condition—A Systematic Review,” Advances in Medical Sciences 65 (2020): 310–315.

[96] V. M. K., P. Jonnada, S. K. N., et al, “Role of Mean Platelet Volume in the Prognosis of Locally Advanced Gastric Cancer: A Tertiary Cancer Center Experience,” Cureus 12 (2020): e9109.

[97] S. Y. Sun, B. Q. Zhao, J. Wang, et al., “The Clinical Implications of Mean Platelet Volume and Mean Platelet Volume/Platelet Count Ratio in Locally Advanced Esophageal Squamous Cell Carcinoma,” Diseases of the Esophagus 31 (2018): dox125.

[98] S. Goksel, N. Ozcelik, G. Telatar, and C. Ardic, “The Role of Hematological Inflammatory Biomarkers in the Diagnosis of Lung Cancer and in Predicting TNM Stage,” Cancer Investigation 39 (2021): 514–520.

[99] W. Xia, W. Chen, J. Tu, C. Ni, and K. Meng, “Prognostic Value and Clinicopathologic Features of Platelet Distribution Width in Cancer: A Meta-Analysis,” Medical Science Monitor 24 (2018): 7130–7136.

[100] A. Karateke, M. Kaplanoglu, and A. Baloglu, “Relations of Platelet Indices With Endometrial Hyperplasia and Endometrial Cancer,” Asian Pacific Journal of Cancer Prevention 16 (2015): 4905–4908.

[101] M. G. Best, N. Sol, I. Kooi, et al., “RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics,” Cancer Cell 28 (2015): 666–676.

[102] R. J. A. Nilsson, L. Balaj, E. Hulleman, et al., “Blood Platelets Contain Tumor-Derived RNA Biomarkers,” Blood 118 (2011): 3680–3683.

[103] L. A. Tjon-Kon-Fat, N. Sol, T. Wurdinger, and R. Nilsson, “Platelet RNA in Cancer Diagnostics,” Seminars in Thrombosis and Hemostasis 44 (2018): 135–141.

[104] G. T. Brown and T. M. McIntyre, “Lipopolysaccharide Signaling Without a Nucleus: Kinase Cascades Stimulate Platelet Shedding of Proinflammatory IL-1β-Rich Microparticles,” Journal of Immunology 186 (2011): 5489–5496.

[105] D. C. Calverley, T. L. Phang, Q. G. Choudhury, et al., “Significant Downregulation of Platelet Gene Expression in Metastatic Lung Cancer,” Clinical and Translational Science 3 (2010): 227–232.

[106] S. Schubert, A. S. Weyrich, and J. W. Rowley, “A Tour Through the Transcriptional Landscape of Platelets,” Blood 124 (2014): 493–502.

[107] N. Arraud, R. Linares, S. Tan, et al., “Extracellular Vesicles From Blood Plasma: Determination of Their Morphology, Size, Phenotype and Concentration,” Journal of Thrombosis and Haemostasis 12 (2014): 614–627.

[108] I. Lopez-Vilchez, M. Diaz-Ricart, A. M. Galan, et al., “Internalization of Tissue Factor-Rich Microvesicles by Platelets Occurs Independently of GPIIb-IIIa, and Involves CD36 Receptor, Serotonin Transporter and Cytoskeletal Assembly,” Journal of Cellular Biochemistry 117 (2016): 448–457.

[109] R. Flaumenhaft, A. Mairuhu, and J. Italiano, “Platelet- and Megakaryocyte-Derived Microparticles,” Seminars in Thrombosis and Hemostasis 36 (2010): 881–887.

[110] M. Żmigrodzka, M. Guzera, A. Miśkiewicz, D. Jagielski, and A. Winnicka, “The Biology of Extracellular Vesicles With Focus on Platelet Microparticles and Their Role in Cancer Development and Progression,” Tumor Biology 37 (2016): 14391–14401.

[111] P. Wolf, “The Nature and Significance of Platelet Products in Human Plasma,” British Journal of Haematology 13 (1967): 269–288.

[112] M. Aatonen, M. Grönholm, and P. Siljander, “Platelet-Derived Microvesicles: Multitalented Participants in Intercellular Communication,” Seminars in Thrombosis and Hemostasis 38 (2012): 102–113.

[113] W. L. Dean, M. J. Lee, T. D. Cummins, D. J. Schultz, and D. W. Powell, “Proteomic and Functional Characterisation of Platelet Microparticle Size Classes,” Thrombosis and Haemostasis 102 (2009): 711–718.

[114] L. Borsig, “Selectins in Cancer Immunity,” Glycobiology 28 (2018): 648–655.

[115] L. J. Gay and B. Felding-Habermann, “Contribution of Platelets to Tumour Metastasis,” Nature Reviews Cancer 11 (2011): 123–134.

[116] S. Schwarz, L. M. Gockel, A. Naggi, et al., “Glycosaminoglycans as Tools to Decipher the Platelet Tumor Cell Interaction: A Focus on P-Selectin,” Molecules 25 (2020): 1039.

[117] Z. Yue, A. Wang, Z. Zhu, et al., “Holothurian Glycosaminoglycan Inhibits Metastasis via Inhibition of P-Selectin in B16F10 Melanoma Cells,” Molecular and Cellular Biochemistry 410 (2015): 143–154.

[118] T. H. Nasti, D. C. Bullard, and N. Yusuf, “P-Selectin Enhances Growth and Metastasis of Mouse Mammary Tumors by Promoting Regulatory T Cell Infiltration Into the Tumors,” Life Sciences 131 (2015): 11–18.

[119] M. Gonzalez-Aparicio and C. Alfaro, “Influence of Interleukin-8 and Neutrophil Extracellular Trap (NET) Formation in the Tumor Microenvironment: Is There a Pathogenic Role?,” Journal of Immunology Research 2019 (2019): 6252138.

[120] S. Lucotti and R. J. Muschel, “Platelets and Metastasis: New Implications of an Old Interplay,” Frontiers in Oncology 10 (2020): 1350.

[121] H. Amano, Y. Ito, F. Ogawa, et al., “Angiotensin II Type 1A Receptor Signaling Facilitates Tumor Metastasis Formation Through P-Selectin-Mediated Interaction of Tumor Cells With Platelets and Endothelial Cells,” American Journal of Pathology 182 (2013): 553–564.

[122] M. Lavergne, E. Janus-Bell, M. Schaff, C. Gachet, and P. Mangin, “Platelet Integrins in Tumor Metastasis: Do They Represent a Therapeutic Target?,” Cancers 9 (2017): 133.

[123] D. Naci, K. Vuori, and F. Aoudjit, “Alpha2beta1 Integrin in Cancer Development and Chemoresistance,” Seminars in Cancer Biology 35 (2015): 145–153.

[124] J. Niu and Z. Li, “The Roles of Integrin αvβ6 in Cancer,” Cancer Letters 403 (2017): 128–137.

[125] J. Huang, X. Li, X. Shi, et al., “Platelet Integrin αIIbβ3: Signal Transduction, Regulation, and Its Therapeutic Targeting,” Journal of Hematology & Oncology 12 (2019): 26.

[126] K. A. Becker, N. Beckmann, C. Adams, et al., “Melanoma Cell Metastasis via P-Selectin-Mediated Activation of Acid Sphingomyelinase in Platelets,” Clinical & Experimental Metastasis 34 (2017): 25–35.

[127] F. Zhao, L. Li, L. Guan, H. Yang, C. Wu, and Y. Liu, “Roles for GP IIb/IIIa and αvβ3 Integrins in MDA-MB-231 Cell Invasion and Shear Flow-Induced Cancer Cell Mechanotransduction,” Cancer Letters 344 (2014): 62–73.

[128] J. W. Semple, J. E. Italiano, , and J. Freedman, “Platelets and the Immune Continuum,” Nature Reviews Immunology 11 (2011): 264–274.

[129] C. Chiodoni, M. Iezzi, C. Guiducci, et al., “Triggering CD40 on Endothelial Cells Contributes to Tumor Growth,” The Journal of Experimental Medicine 203 (2006): 2441–2450.

[130] J. W. Rowley, H. Schwertz, and A. S. Weyrich, “Platelet mRNA: the Meaning Behind the Message,” Current Opinion in Hematology 19 (2012): 385–391.

[131] S. Amisten, “A Rapid and Efficient Platelet Purification Protocol for Platelet Gene Expression Studies,” Methods in Molecular Biology 788 (2012): 155–172.

[132] P. Harrison and A. H. Goodall, “Message in the Platelet”—More Than Just Vestigial mRNA!,” Platelets 19 (2008): 395–404.

[133] M. G. Best, N. Sol, S. G. J. G. In ‘t Veld, et al., “Swarm Intelligence-Enhanced Detection of Non-Small-Cell Lung Cancer Using Tumor-Educated Platelets,” Cancer Cell 32 (2017): 238–252.

[134] A. A. Alhasan, O. G. Izuogu, H. H. Al-Balool, et al., “Circular RNA Enrichment in Platelets Is a Signature of Transcriptome Degradation,” Blood 127 (2016): e1–e11.

[135] N. Sunderland, P. Skroblin, T. Barwari, et al., “MicroRNA Biomarkers and Platelet Reactivity: The Clot Thickens,” Circulation Research 120 (2017): 418–435.

[136] S. Dahariya, I. Paddibhatla, S. Kumar, S. Raghuwanshi, A. Pallepati, and R. K. Gutti, “Long Non-Coding RNA: Classification, Biogenesis and Functions in Blood Cells,” Molecular Immunology 112 (2019): 82–92.

[137] S. Nagalla, C. Shaw, X. Kong, et al., “Platelet microRNA-mRNA Coexpression Profiles Correlate With Platelet Reactivity,” Blood 117 (2011): 5189–5197.

[138] E. Boerrigter, L. N. Groen, N. P. Van Erp, G. W. Verhaegh, and J. A. Schalken, “Clinical Utility of Emerging Biomarkers in Prostate Cancer Liquid Biopsies,” Expert Review of Molecular Diagnostics 20 (2020): 219–230.

[139] N. Dahiya, T. Sarachana, L. Vu, et al., “Platelet MicroRNAs: An Overview,” Transfusion Medicine Reviews 29 (2015): 215–219.

[140] M. Saboor, Q. Ayub, S. Ilyas, and Moinuddin , “Platelet Receptors; an Instrumental of Platelet Physiology,” Pakistan Journal of Medical Sciences 29 (2013): 891–896.

[141] C. Looße, F. Swieringa, J. W. M. Heemskerk, A. Sickmann, and C. Lorenz, “Platelet Proteomics: From Discovery to Diagnosis,” Expert Review of Proteomics 15 (2018): 467–476.

[142] S. Najafi, Y. Asemani, J. Majidpoor, R. Mahmoudi, S. M. Aghaei-Zarch, and K. Mortezaee, “Tumor-Educated Platelets,” Clinica Chimica Acta 552 (2024): 117690.

[143] A. H. Qureshi, V. Chaoji, D. Maiguel, et al., “Proteomic and Phospho-Proteomic Profile of Human Platelets in Basal, Resting State: Insights Into Integrin Signaling,” PLoS One 4 (2009): e7627.

[144] A. S. Weyrich, H. Schwertz, L. W. Kraiss, and G. A. Zimmerman, “Protein Synthesis by Platelets: Historical and New Perspectives,” Journal of Thrombosis and Haemostasis 7 (2009): 241–246.

[145] D. Boyanova, S. Nilla, I. Birschmann, T. Dandekar, and M. Dittrich, “Plateletweb: A Systems Biologic Analysis of Signaling Networks in Human Platelets,” Blood 119 (2012): e22-34.

[146] A. T. Franco, A. Corken, and J. Ware, “Platelets at the Interface of Thrombosis, Inflammation, and Cancer,” Blood 126 (2015): 582–588.

[147] S. Lazar and L. E. Goldfinger, “Platelet Microparticles and miRNA Transfer in Cancer Progression: Many Targets, Modes of Action, and Effects Across Cancer Stages,” Frontiers in Cardiovascular Medicine 5 (2018): 13.

[148] Y. Pan, H. Liang, H. Liu, et al., “Platelet-Secreted microRNA-223 Promotes Endothelial Cell Apoptosis Induced by Advanced Glycation End Products via Targeting the Insulin-Like Growth Factor 1 Receptor,” Journal of Immunology 192 (2014): 437–446.

[149] H. Liang, X. Yan, Y. Pan, et al., “MicroRNA-223 Delivered by Platelet-Derived Microvesicles Promotes Lung Cancer Cell Invasion via Targeting Tumor Suppressor Epb41l3,” Molecular Cancer 14 (2015): 58.

[150] D. Mege, L. Panicot-Dubois, M. Ouaissi, et al., “The Origin and Concentration of Circulating Microparticles Differ According to Cancer Type and Evolution: A Prospective Single-Center Study,” International Journal of Cancer 138 (2016): 939–948.

[151] S. Xing, T. Zeng, N. Xue, et al., “Development and Validation of Tumor-Educated Blood Platelets Integrin Alpha 2b (ITGA2B) RNA for Diagnosis and Prognosis of Non-Small-Cell Lung Cancer Through RNA-Seq,” International Journal of Biological Sciences 15 (2019): 1977–1992.

[152] L. Liu, X. Song, X. Li, et al., “A Three-Platelet mRNA Set: MAX, MTURN and HLA-B as Biomarker for Lung Cancer,” Journal of Cancer Research and Clinical Oncology 145 (2019): 2713–2723.

[153] B. Yao, S. Qu, R. Hu, et al., “Delivery of Platelet TPM3 mRNA Into Breast Cancer Cells via Microvesicles Enhances Metastasis,” FEBS Open Bio 9 (2019): 2159–2169.

[154] L. Yang, Q. Jiang, D. Z. Li, X. Zhou, D. S. Yu, and J. Zhong, “TIMP1 mRNA in Tumor-Educated Platelets Is Diagnostic Biomarker for Colorectal Cancer,” Aging 11 (2019): 8998–9012.

[155] R. J. A. Nilsson, N. Karachaliou, J. Berenguer, et al., “Rearranged EML4-ALK Fusion Transcripts Sequester in Circulating Blood Platelets and Enable Blood-Based Crizotinib Response Monitoring in Non-Small-Cell Lung Cancer,” Oncotarget 7 (2016): 1066–1075.

[156] L. Xu, X. Li, X. Li, et al., “Rna Profiling of Blood Platelets Noninvasively Differentiates Colorectal Cancer From Healthy Donors and Noncancerous Intestinal Diseases: A Retrospective Cohort Study,” Genome Medicine 14 (2022): 26.

[157] Y. Gao, C. J. Liu, H. Y. Li, et al., “Platelet RNA Enables Accurate Detection of Ovarian Cancer: An Intercontinental, Biomarker Identification Study,” Protein & Cell 14 (2023): 579–590.

[158] X. Li, L. Liu, X. Song, et al., “TEP linc-GTF2H2-1, RP3-466P17.2, and lnc-ST8SIA4-12 as Novel Biomarkers for Lung Cancer Diagnosis and Progression Prediction,” Journal of Cancer Research and Clinical Oncology 147 (2021): 1609–1622.

[159] X. Dong, X. Song, S. Ding, et al., “Tumor-Educated Platelet SNORD55 as a Potential Biomarker for the Early Diagnosis of Non-Small Cell Lung Cancer,” Thoracic Cancer 12 (2021): 659–666.

[160] X. Dong, S. Ding, M. Yu, et al., “Small Nuclear RNAs (U1, U2, U5) in Tumor-Educated Platelets Are Downregulated and Act as Promising Biomarkers in Lung Cancer,” Frontiers in Oncology 10 (2020): 1627.

[161] N. Sol, S. G. J. G. in ‘t Veld, A. Vancura, et al., “Tumor-Educated Platelet RNA for the Detection and (Pseudo)Progression Monitoring of Glioblastoma,” Cell Reports Medicine 1 (2020): 100101.

[162] B. Ye, F. Li, M. Chen, et al., “A Panel of Platelet-Associated Circulating Long Non-Coding RNAs as Potential Biomarkers for Colorectal Cancer,” Genomics 114 (2022): 31–37.

[163] Y. Xu, L. Chen, Y. Chen, et al., “Prediction of Potential Biomarkers in Early-Stage Nasopharyngeal Carcinoma Based on Platelet RNA Sequencing,” Molecular Biotechnology 65 (2023): 1096–1108.

[164] S. Takagi, S. Tsukamoto, J. Park, et al., “Platelets Enhance Multiple Myeloma Progression via IL-1β Upregulation,” Clinical Cancer Research 24 (2018): 2430–2439.

[165] J. E. Peterson, D. Zurakowski, J. E. Italiano, , et al., “VEGF, PF4 and PDGF Are Elevated in Platelets of Colorectal Cancer Patients,” Angiogenesis 15 (2012): 265–273.

[166] S. Strohkamp, T. Gemoll, S. Humborg, et al., “Protein Levels of Clusterin and Glutathione Synthetase in Platelets Allow for Early Detection of Colorectal Cancer,” Cellular and Molecular Life Sciences 75 (2018): 323–334.

[167] C. Hinterleitner, J. Strähle, E. Malenke, et al., “Platelet PD-L1 Reflects Collective Intratumoral PD-L1 Expression and Predicts Immunotherapy Response in Non-Small Cell Lung Cancer,” Nature Communications 12 (2021): 7005.

[168] M. G. Best, S. G. J. G. In ‘t Veld, N. Sol, and T. Wurdinger, “RNA Sequencing and Swarm Intelligence-Enhanced Classification Algorithm Development for Blood-Based Disease Diagnostics Using Spliced Blood Platelet RNA,” Nature Protocols 14 (2019): 1206–1234.

[169] K. M. Heinhuis, S. G. J. G. In ‘t Veld, G. Dwarshuis, et al., “RNA-Sequencing of Tumor-Educated Platelets, a Novel Biomarker for Blood-Based Sarcoma Diagnostics,” Cancers 12 (2020): 1372.

[170] M. Sheng, Z. Dong, and Y. Xie, “Identification of Tumor-Educated Platelet Biomarkers of Non-Small-Cell Lung Cancer,” OncoTargets and Therapy 11 (2018): 8143–8151.

[171] T. N. Beck, Y. A. Boumber, C. Aggarwal, et al., “Circulating Tumor Cell and Cell-Free RNA Capture and Expression Analysis Identify Platelet-Associated Genes in Metastatic Lung Cancer,” BMC Cancer 19 (2019): 603.

[172] S. Sabrkhany, M. J. E. Kuijpers, J. C. Knol, et al., “Exploration of the Platelet Proteome in Patients With Early-Stage Cancer,” Journal of Proteomics 177 (2018): 65–74.

[173] M. Lomnytska, R. Pinto, S. Becker, et al., “Platelet Protein Biomarker Panel for Ovarian Cancer Diagnosis,” Biomarker Research 6 (2018): 2.

[174] M. Walraven, S. Sabrkhany, J. Knol, et al., “Effects of Cancer Presence and Therapy on the Platelet Proteome,” International Journal of Molecular Sciences 22 (2021): 8236.

[175] Y. Ke, Z. Ma, H. Ye, et al., “Chlorogenic Acid-Conjugated Nanoparticles Suppression of Platelet Activation and Disruption to Tumor Vascular Barriers for Enhancing Drug Penetration in Tumor,” Advanced Healthcare Materials 12 (2023): e2202205.

[176] Z. Ma, S. Liu, Y. Ke, et al., “Biomimetic Nano-NOS Mediated Local NO Release for Inhibiting Cancer-Associated Platelet Activation and Disrupting Tumor Vascular Barriers,” Biomaterials 255 (2020): 120141.

[177] Y. Wang, C. Jian, Y. Long, X. Xu, Y. Song, and Z. Yin, “H(2)O(2)-triggered “Off/On Signal” Nanoparticles Target P-Selectin for the Non-Invasive and Contrast-Enhanced Theranostics for Arterial Thrombosis,” Acta Biomaterialia 158 (2023): 769–781.

[178] X. Zhang, X. Li, S. Sun, et al., “Anti-Tumor Metastasis via Platelet Inhibitor Combined With Photothermal Therapy Under Activatable Fluorescence/Magnetic Resonance Bimodal Imaging Guidance,” ACS Applied Materials & Interfaces 13 (2021): 19679–19694.

[179] J. Cao, P. Yang, P. Wang, et al., “Adhesion and Release' Nanoparticle-Mediated Efficient Inhibition of Platelet Activation Disrupts Endothelial Barriers for Enhanced Drug Delivery in Tumors,” Biomaterials 269 (2021): 120620.

[180] L. H. Chang, E. Y. Chuang, T. M. Cheng, et al., “Thrombus-Specific Theranostic Nanocomposite for Codelivery of Thrombolytic Drug, Algae-Derived Anticoagulant and NIR Fluorescent Contrast Agent,” Acta Biomaterialia 134 (2021): 686–701.

[181] S. Li, Y. Zhang, J. Wang, et al., “Nanoparticle-Mediated Local Depletion of Tumour-Associated Platelets Disrupts Vascular Barriers and Augments Drug Accumulation in Tumours,” Nature Biomedical Engineering 1 (2017): 667–679.

[182] S. Wang, N. Yin, Y. Li, et al., “Copper-Based Metal-Organic Framework Impedes Triple-Negative Breast Cancer Metastasis via Local Estrogen Deprivation and Platelets Blockade,” Journal of Nanobiotechnology 20 (2022): 313.

[183] Y. Xu, J. Liu, Z. Liu, et al., “Blockade of Platelets Using Tumor-Specific NO-Releasing Nanoparticles Prevents Tumor Metastasis and Reverses Tumor Immunosuppression,” ACS Nano 14 (2020): 9780–9795.

[184] Y. Zhang, J. Wei, S. Liu, et al., “Inhibition of Platelet Function Using Liposomal Nanoparticles Blocks Tumor Metastasis,” Theranostics 7 (2017): 1062–1071.

[185] Y. Wang, W. Li, Z. Li, et al., “Active Recruitment of Anti-PD-1-Conjugated Platelets Through Tumor-Selective Thrombosis for Enhanced Anticancer Immunotherapy,” Science Advances 9 (2023): eadf6854.

[186] C. Huang, S. Ding, W. Jiang, and F. B. Wang, “Glutathione-Depleting Nanoplatelets for Enhanced Sonodynamic Cancer Therapy,” Nanoscale 13 (2021): 4512–4518.

[187] H. Wang, J. Wu, G. R. Williams, et al., “Platelet-Membrane-Biomimetic Nanoparticles for Targeted Antitumor Drug Delivery,” Journal of Nanobiotechnology 17 (2019): 60.

[188] D. Ren, G. R. Williams, Y. Zhang, R. Ren, J. Lou, and L. M. Zhu, “Mesoporous Doxorubicin-Loaded Polydopamine Nanoparticles Coated With a Platelet Membrane Suppress Tumor Growth in a Murine Model of Human Breast Cancer,” ACS Applied Bio Materials 5 (2022): 123–133.

[189] P. Qi, J. Zhang, Z. Bao, Y. Liao, Z. Liu, and J. Wang, “A Platelet-Mimicking Single-Atom Nanozyme for Mitochondrial Damage-Mediated Mild-Temperature Photothermal Therapy,” ACS Applied Materials & Interfaces 14 (2022): 19081–19090.

[190] J. Zou, J. He, X. Wang, et al., “Glycoprotein Ib-Regulated Micro Platelet Ghost for Biosafe Distribution and Photothermal Oncotherapy,” Journal of Controlled Release 351 (2022): 341–360.

[191] S. Wan, Q. Fan, Y. Wu, et al., “Curcumin-Loaded Platelet Membrane Bioinspired Chitosan-Modified Liposome for Effective Cancer Therapy,” Pharmaceutics 15 (2023): 631.

[192] S. Ning, T. Zhang, M. Lyu, et al., “A Type I AIE Photosensitiser-Loaded Biomimetic Nanosystem Allowing Precise Depletion of Cancer Stem Cells and Prevention of Cancer Recurrence After Radiotherapy,” Biomaterials 295 (2023): 122034.

[193] H. Yan, Y. Zhang, Y. Zhang, et al., “A ROS-Responsive Biomimetic Nano-Platform for Enhanced Chemo-Photodynamic-Immunotherapy Efficacy,” Biomaterials Science 10 (2022): 6583–6600.

[194] L. Li, J. Fu, X. Wang, et al., “Biomimetic ‘Nanoplatelets’ as a Targeted Drug Delivery Platform for Breast Cancer Theranostics,” ACS Applied Materials & Interfaces 13 (2021): 3605–3621.

[195] Y. Chen, X. Shen, S. Han, et al., “Irradiation Pretreatment Enhances the Therapeutic Efficacy of Platelet-Membrane-Camouflaged Antitumor Nanoparticles,” Journal of Nanobiotechnology 18 (2020): 101.

[196] X. Luo, J. Cao, J. Yu, et al., “Regulating Acidosis and Relieving Hypoxia by Platelet Membrane-Coated Nanoparticle for Enhancing Tumor Chemotherapy,” Frontiers in Bioengineering and Biotechnology 10 (2022): 885105.

[197] Y. Du, S. Wang, J. Luan, et al., “Gox-Functionalized Platelet Membranes-Camouflaging Nanoreactors for Enhanced Multimodal Tumor Treatment,” International Journal of Nanomedicine 17 (2022): 2979–2993.

[198] W. Pei, B. Huang, S. Chen, et al, “Platelet-Mimicking Drug Delivery Nanoparticles for Enhanced Chemo-Photothermal Therapy of Breast Cancer,” International Journal of Nanomedicine 15 (2020): 10151–10167.

[199] Q. Lu, H. Ye, K. Wang, et al., “Bioengineered Platelets Combining Chemotherapy and Immunotherapy for Postsurgical Melanoma Treatment: Internal Core-Loaded Doxorubicin and External Surface-Anchored Anti-PD-L1 Antibody Backpacks,” Nano Letters 22 (2022): 3141–3150.

[200] Q. R. Li, H. Z. Xu, R. C. Xiao, et al., “Laser-Triggered Intelligent Drug Delivery and Anti-Cancer Photodynamic Therapy Using Platelets as the Vehicle,” Platelets 34 (2023): 2166677.

[201] L. Zhou, W. Feng, Y. Mao, Y. Chen, and X. Zhang, “Nanoengineered Sonosensitive Platelets for Synergistically Augmented Sonodynamic Tumor Therapy by Glutamine Deprivation and Cascading Thrombosis,” Bioactive Materials 24 (2023): 26–36.

[202] Y. Zhang, Y. Sun, X. Dong, et al., “A Platelet Intelligent Vehicle With Navigation for Cancer Photothermal-Chemotherapy,” ACS Nano 16 (2022): 6359–6371.

[203] Q. Hu, H. Li, E. Archibong, et al., “Inhibition of Post-Surgery Tumour Recurrence via a Hydrogel Releasing CAR-T Cells and anti-PDL1-Conjugated Platelets,” Nature Biomedical Engineering 5 (2021): 1038–1047.

[204] Y. Gao, X. Chen, B. Wang, et al., “Engineering Platelets With PDL1 Antibodies and Iron Oxide Nanoparticles for Postsurgical Cancer Immunotherapy,” ACS Applied Bio Materials 6 (2023): 257–266.

[205] T. Nishikawa, L. Y. Tung, and Y. Kaneda, “Systemic Administration of Platelets Incorporating Inactivated Sendai Virus Eradicates Melanoma in Mice,” Molecular Therapy 22 (2014): 2046–2055.

[206] L. Jing, H. Qu, D. Wu, et al., “Platelet-Camouflaged Nanococktail: Simultaneous Inhibition of Drug-Resistant Tumor Growth and Metastasis via a Cancer Cells and Tumor Vasculature Dual-Targeting Strategy,” Theranostics 8 (2018): 2683–2695.

[207] A. L. Papa, A. Jiang, N. Korin, et al., “Platelet Decoys Inhibit Thrombosis and Prevent Metastatic Tumor Formation in Preclinical Models,” Science Translational Medicine 11 (2019): eaau5898.

[208] Z. Zhou, B. Zhang, W. Zai, et al., “Perfluorocarbon Nanoparticle-Mediated Platelet Inhibition Promotes Intratumoral Infiltration of T Cells and Boosts Immunotherapy,” Proceedings of the National Academy of Sciences 116 (2019): 11972–11977.

[209] C. M. J. Hu, R. H. Fang, K. C. Wang, et al., “Nanoparticle Biointerfacing by Platelet Membrane Cloaking,” Nature 526 (2015): 118–121.

[210] J. Li, Y. Ai, L. Wang, et al., “Targeted Drug Delivery to Circulating Tumor Cells via Platelet Membrane-Functionalized Particles,” Biomaterials 76 (2016): 52–65.

[211] J. Li, C. C. Sharkey, B. Wun, J. L. Liesveld, and M. R. King, “Genetic Engineering of Platelets to Neutralize Circulating Tumor Cells,” Journal of Controlled Release 228 (2016): 38–47.

[212] J. Zhuang, H. Gong, J. Zhou, et al., “Targeted Gene Silencing In Vivo by Platelet Membrane-Coated Metal-Organic Framework Nanoparticles,” Science Advances 6 (2020): eaaz6108.

[213] D. Cacic, T. Hervig, and H. Reikvam, “Platelets for Advanced Drug Delivery in Cancer,” Expert Opinion on Drug Delivery 20 (2023): 673–688.

[214] D. Xia, D. Hang, Y. Li, et al., “Au-Hemoglobin Loaded Platelet Alleviating Tumor Hypoxia and Enhancing the Radiotherapy Effect With Low-Dose X-ray,” ACS Nano 14 (2020): 15654–15668.

[215] H. Z. Xu, T. F. Li, Y. Ma, et al., “Targeted Photodynamic Therapy of Glioblastoma Mediated by Platelets With Photo-Controlled Release Property,” Biomaterials 290 (2022): 121833.

[216] Y. Chen, S. Pal, W. Li, F. Liu, S. Yuan, and Q. Hu, “Engineered Platelets as Targeted Protein Degraders and Application to Breast Cancer Models,” Nature Biotechnology, ahead of print, December 3, 2024.

[217] S. D'Ambrosi, R. J. Nilsson, and T. Wurdinger, “Platelets and Tumor-Associated RNA Transfer,” Blood 137 (2021): 3181–3191.

[218] J. Johnson, Y. W. Wu, C. Blyth, G. Lichtfuss, H. Goubran, and T. Burnouf, “Prospective Therapeutic Applications of Platelet Extracellular Vesicles,” Trends in Biotechnology 39 (2021): 598–612.

[219] C. Yao and C. Wang, “Platelet-Derived Extracellular Vesicles for Drug Delivery,” Biomaterials Science 11 (2023): 5758–5768.

[220] J. V. Michael, J. G. T. Wurtzel, G. F. Mao, et al., “Platelet Microparticles Infiltrating Solid Tumors Transfer miRNAs That Suppress Tumor Growth,” Blood 130 (2017): 567–580.

[221] R. Li, Y. He, S. Zhang, J. Qin, and J. Wang, “Cell Membrane-Based Nanoparticles: A New Biomimetic Platform for Tumor Diagnosis and Treatment,” Acta Pharmaceutica Sinica B 8 (2018): 14–22.

[222] E. Sinauridze, D. Kireev, N. Popenko, et al., “Platelet Microparticle Membranes Have 50- to 100-fold Higher Specific Procoagulant Activity Than Activated Platelets,” Thrombosis and Haemostasis 97 (2007): 425–434.

[223] S. Mookerjee, H. R. Foster, A. K. Waller, and C. J. Ghevaert, “In Vitro-Derived Platelets: The Challenges We Will Have to Face to Assess Quality and Safety,” Platelets 31 (2020): 724–730.

[224] The Cancer Genome Atlas Network, Comprehensive Molecular Portraits of Human Breast Tumours,” Nature 490 (2012): 61–70.

[225] L. Clancy and J. E. Freedman, “New Paradigms in Thrombosis: Novel Mediators and Biomarkers Platelet RNA Transfer,” Journal of Thrombosis and Thrombolysis 37 (2014): 12–16.

[226] M. Kirschbaum, G. Karimian, J. Adelmeijer, B. N. G. Giepmans, R. J. Porte, and T. Lisman, “Horizontal RNA Transfer Mediates Platelet-Induced Hepatocyte Proliferation,” Blood 126 (2015): 798–806.

[227] K. C. Wong, J. Chen, J. Zhang, et al., “Early Cancer Detection From Multianalyte Blood Test Results,” iScience 15 (2019): 332–341.

[228] A. Halner, L. Hankey, Z. Liang, et al., “DEcancer: Machine Learning Framework Tailored to Liquid Biopsy Based Cancer Detection and Biomarker Signature Selection,” iScience 26 (2023): 106610.

[229] J. D. Cohen, L. Li, Y. Wang, et al., “Detection and Localization of Surgically Resectable Cancers With a Multi-Analyte Blood Test,” Science 359 (2018): 926–930.

[230] A. Eledkawy, T. Hamza, and S. El-Metwally, “Precision Cancer Classification Using Liquid Biopsy and Advanced Machine Learning Techniques,” Scientific Reports 14 (2024): 5841.

[231] S. Cygert, K. Pastuszak, F. Górski, et al., “Platelet-Based Liquid Biopsies Through the Lens of Machine Learning,” Cancers 15 (2023): 2336.

RIGHTS & PERMISSIONS

2025 The Author(s). MedComm - Biomaterials and Applications published by John Wiley & Sons Australia, Ltd on behalf of Sichuan International Medical Exchange & Promotion Association (SCIMEA).