Exploration of Medicine

From: Nanomedicine in cancer therapy: promises and hurdles of polymeric nanoparticles

Table 2. Examples of clinically approved nanomedicine

Year of approval	Name	Nanotechnology platform	Therapeutic agent	Indication	Refs
1995 (FDA) 1996 (EMA)	Doxil/Caelyx	Liposome (PEGylated)	Doxorubicin	HIV-associated Kaposi sarcoma, ovarian cancer, metastatic breast cancer, multiple myeloma	[9]
1996 (FDA)	DaunoXome	Liposome (non-PEGylated	Daunorubicin	HIV-associated Kaposi sarcoma	[10]
2002 (FDA)	Eligard	poly(D, L-Lactide-co-glycolide) (PLGH)	Leuprorelin acetate	Prostate cancer	[11]
2005 (FDA) 2008 (EMA)	Abraxane	Nanoparticle albumin bound	Paclitaxel	Advanced non-small-cell lung cancer, metastatic breast cancer, metastatic pancreatic cancer	[12]
2006 (FDA)	Oncaspar	polyethyleneglycol (PEG) protein conjugate	L-asparaginase	Leukemia	[13]
2009 (EMA)	MEPACT	Liposome (non-PEGylated)	Mifamurtide	Osteosarcoma	[14]
2015 (FDA)	MM-398/Onivyde	Liposome (PEGylated)	Irinotecan	Metastatic pancreatic cancer	[15]
2017 (FDA)	VYXEOS	Liposome	Daunorubicin and cytarabine	Acute myeloid leukemia	[16]
2019 (FDA)	Polivy (polatuzumab vedotin-piiq)	Antibody-drug conjugate	Monomethyl auristatin E	Relapsed diffuse large B-cell lymphoma	[17]

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FDA: Food and Drug Administration; EMA: European Medicines Agency

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References

Gerlinger M, Swanton C. How darwinian models inform therapeutic failure initiated by clonal heterogeneity in cancer medicine. Br J Cancer. 2010;103:1139–43. [DOI]

Gottesman MM. Mechanisms of cancer drug resistance. Annu Rev Med. 2002;53:615–27. [DOI] [PubMed]

Lungu II, Grumezescu AM, Volceanov A, Andronescu E. Nanobiomaterials used in cancer therapy: an up-to-date overview. molecules 2019;24:3547. [DOI]

Stylianopoulos T, Jain RK. Design considerations for nanotherapeutics in oncology. Nanomedicine. 2015;11:1893–907. [DOI] [PubMed] [PMC]

Piktel E, Niemirowicz K, Watek M, Wollny T, Deptula P, Bucki R. Recent insights in nanotechnology-based drugs and formulations designed for effective anti-cancer therapy. J Nanobiotechnology. 2016;14:39. [DOI] [PubMed] [PMC]

Zhang X, Wang Q, Qin L, Fu H, Fang Y, Han B, et al. EGF-modified mPEG-PLGA-PLL nanoparticle for delivering doxorubicin combined with Bcl-2 siRNA as a potential treatment strategy for lung cancer. Drug Deliv. 2016;23:2936–45. [DOI]

Mitsunaga M, Ogawa M, Kosaka N, Rosenblum LT, Choyke PL, Kobayashi H. Cancer cell-selective in vivo near infrared photoimmunotherapy targeting specific membrane molecules. Nat Med. 2012;17:1685–91. [DOI]

Hammink R, Mandal S, Eggermont LJ, Nooteboom M, Willems PH, Tel J, et al. Controlling T-cell activation with synthetic dendritic cells using the multivalency effect. ACS Omega. 2017;2:937–45. [DOI] [PubMed] [PMC]

Barenholz YC. Doxil®—the first FDA-approved nano-drug: lessons learned. J Control Release. 2012;160:117–34. [DOI]

10.

Rosenthal E, Poizot-Martin I, Saint-Marc T, Spano JP, Cacoub P, Group DS. Phase IV study of liposomal daunorubicin (DaunoXome) in AIDS-related Kaposi sarcoma. Am J Clin Oncol. 2002;25:57–9. [DOI]

11.

Braeckman J, Michielsen D. Efficacy and tolerability of 1- and 3-month leuprorelin acetate depot formulations (Eligard®/Depo-Eligard®) for advanced prostate cancer in daily practice: a Belgian prospective non-interventional study. Arch Med Sci. 2014;10:477–83. [DOI]

12.

Saif MW. US Food and Drug Administration approves paclitaxel protein-bound particles (Abraxane®) in combination with gemcitabine as first-line treatment of patients with metastatic pancreatic cancer. JOP. 2013;14:686–8.

13.

Dinndorf PA, Gootenberg J, Cohen MH, Keegan P, Pazdur R. FDA drug approval summary: pegaspargase (Oncaspar®) for the first-line treatment of children with acute lymphoblastic leukemia (ALL). Oncologist. 2007;12:991–8. [DOI]

14.

Meyers PA. Muramyl tripeptide (mifamurtide) for the treatment of osteosarcoma. Expert Rev Anticancer Ther. 2009;9:1035–49. [DOI] [PubMed]

15.

Zhang H. Onivyde for the therapy of multiple solid tumors. Onco Targets Ther. 2016;9:3001. [DOI] [PubMed] [PMC]

16.

Nikanjam M, Capparelli EV, Lancet JE, Louie A, Schiller G. Persistent cytarabine and daunorubicin exposure after administration of novel liposomal formulation CPX-351: population pharmacokinetic assessment. Cancer Chemother Pharmacol. 2018;81:171–8. [DOI]

17.

Deeks ED. Polatuzumab vedotin: ffirst global approval. Drugs. 2019;79:1467–75. [DOI]

18.

Bobo D, Robinson KJ, Islam J, Thurecht KJ, Corrie SR. Nanoparticle-based medicines: a review of FDA-approved materials and clinical trials to date. Pharm Res. 2016;33:2373–87. [DOI]

19.

Caster JM, Patel AN, Zhang T, Wang A. Investigational nanomedicines in 2016: a review of nanotherapeutics currently undergoing clinical trials. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2017;9. [DOI]

20.

Gabizon A, Shiota R, Papahadjopoulos D. Pharmacokinetics and tissue distribution of doxorubicin encapsulated in stable liposomes with long circulation times. J Natl Cancer Inst. 1989;81:1484–8. [DOI]

21.

Theodoulou M, Batist G, Campos S, Winer E, Welles L, Hudis C. Phase I study of nonpegylated liposomal doxorubicin plus trastuzumab in patients with HER2-positive breast cancer. Clin Breast Cancer. 2009;9:101–7. [DOI] [PubMed]

22.

Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer. 2003;97:2869–79. [DOI]

23.

Uziely B, Jeffers S, Isacson R, Kutsch K, Wei-Tsao D, Yehoshua Z, et al. Liposomal doxorubicin: antitumor activity and unique toxicities during two complementary phase I studies. J Clin Oncol. 1995;13:1777–85. [DOI]

24.

Muggia FM, Hainsworth JD, Jeffers S, Miller P, Groshen S, Tan M, et al. Phase II study of liposomal doxorubicin in refractory ovarian cancer: antitumor activity and toxicity modification by liposomal encapsulation. J Clin Oncol. 1997;15:987–93. [DOI]

25.

Safra T, Muggia F, Jeffers S, Tsao-Wei D, Groshen S, Lyass O, et al. Pegylated liposomal doxorubicin (doxil): reduced clinical cardiotoxicity in patients reaching or exceeding cumulative doses of 500 mg/m². Ann Oncol. 2000;11:1029–33. [DOI]

26.

Wagner U, Marth C, Largillier R, Kaern J, Brown C, Heywood M, et al. Final overall survival results of phase III GCIG CALYPSO trial of pegylated liposomal doxorubicin and carboplatin vs paclitaxel and carboplatin in platinum-sensitive ovarian cancer patients. Br J Cancer. 2012;107:588–91. [DOI]

27.

Halm U, Etzrodt G, Schiefke I, Schmidt F, Witzigmann H, Mössner J, et al. A phase II study of pegylated liposomal doxorubicin for treatment of advanced hepatocellular carcinoma. Ann of Oncol. 2000;11: 113–4. [DOI]

28.

O’brien M, Wigler N, Inbar M, Rosso R, Grischke E, Santoro A, et al. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX™/Doxil®) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol. 2004;15:440–9. [DOI]

29.

Mishra S, Webster P, Davis ME. PEGylation significantly affects cellular uptake and intracellular trafficking of non-viral gene delivery particles. Eur J Cell Biol. 2004;83:97–111. [DOI]

30.

Rehman Zu, Hoekstra D, Zuhorn IS. Mechanism of polyplex-and lipoplex-mediated delivery of nucleic acids: real-time visualization of transient membrane destabilization without endosomal lysis. ACS Nano. 2013;7:3767–77. [DOI] [PubMed]

31.

Urban-Klein B, Werth S, Abuharbeid S, Czubayko F, Aigner A. RNAi-mediated gene-targeting through systemic application of polyethylenimine (PEI)-complexed siRNA in vivo. Gene Ther. 2005;12:461–6. [DOI]

32.

Ragelle H, Danhier F, Préat V, Langer R, Anderson DG. Nanoparticle-based drug delivery systems: a commercial and regulatory outlook as the field matures. Expert Opin Drug Deliv. 2017;14:851–64. [DOI]

33.

Arnold AE, Czupiel P, Shoichet M. Engineered polymeric nanoparticles to guide the cellular internalization and trafficking of small interfering ribonucleic acids. J Control Release. 2017;259:3–15. [DOI]

34.

Vermeulen LMP, Brans T, Samal SK, Dubruel P, Demeester J, De Smedt SC, et al. Endosomal size and membrane leakiness influence proton sponge-based rupture of endosomal vesicles. ACS Nano. 2018;12:2332–45. [DOI]

35.

Rejman J, Conese M, Hoekstra D. Gene transfer by means of lipo-and polyplexes: role of clathrin and caveolae-mediated endocytosis. J Liposome Res. 2006;16:237–47. [DOI]

36.

Agarwal S, Zhang Y, Maji S, Greiner A. PDMAEMA based gene delivery materials. Materials Today. 2012;15:388–93. [DOI]

37.

Cheng Q, Du L, Meng L, Han S, Wei T, Wang X, et al. The promising nanocarrier for doxorubicin and siRNA co-delivery by PDMAEMA-based amphiphilic nanomicelles. ACS Appl Mater Interfaces. 2016;8:4347–56. [DOI] [PubMed]

38.

Wittrup A, Ai A, Liu X, Hamar P, Trifonova R, Charisse K, et al. Visualizing lipid-formulated siRNA release from endosomes and target gene knockdown. Nat Biotechnol. 2015;33:870–6. [DOI]

39.

Li Z, Chen G, Ding L, Wang Y, Zhu C, Wang K, et al. Increased survival by pulmonary treatment of established lung metastases with dual STAT3/CXCR4 inhibition by siRNA nanoemulsions. Mol Ther. 2019;27:2100–10. [DOI]

40.

Babu A, Muralidharan R, Amreddy N, Mehta M, Munshi A, Ramesh R. Nanoparticles for siRNA-based gene silencing in tumor therapy. IEEE Trans Nanobioscience. 2016;15:849–63. [DOI]

41.

Parvani JG, Jackson MW. Silencing the roadblocks to effective triple-negative breast cancer treatments by siRNA nanoparticles. Endocr Relat Cancer. 2017;24:R81–97. [DOI]

42.

Foroozandeh P, Aziz AA. Insight into Cellular Uptake and Intracellular Trafficking of Nanoparticles. Nanoscale research letters. 2018;13:339. [DOI] [PubMed] [PMC]

43.

Blanco E, Shen H, Ferrari M. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat Biotechnol. 2015;33:941–51. [DOI]

44.

Xin X, Teng C, Du X, Lv Y, Xiao Q, Wu Y, et al. Drug-delivering-drug platform-mediated potent protein therapeutics via a non-endo-lysosomal route. Theranostics. 2018;8:3474–89. [DOI] [PubMed] [PMC]

45.

Zhang L, Yang X, Lv Y, Xin X, Qin C, Han X, et al. Cytosolic co-delivery of miRNA-34a and docetaxel with core-shell nanocarriers via caveolae-mediated pathway for the treatment of metastatic breast cancer. Sci Rep. 2017;7:46186. [DOI] [PubMed] [PMC]

46.

Bar-Zeev M, Livney YD, Assaraf YG. Targeted nanomedicine for cancer therapeutics: towards precision medicine overcoming drug resistance. Drug Resist Updat. 2017;31:15–30. [DOI]

47.

Liu J, Wei T, Zhao J, Huang Y, Deng H, Kumar A, et al. Multifunctional aptamer-based nanoparticles for targeted drug delivery to circumvent cancer resistance. Biomaterials. 2016;91:44–56. [DOI]

48.

Yu S, Bi X, Yang L, Wu S, Yu Y, Jiang B, et al. Co-delivery of paclitaxel and PLK1-targeted siRNA using aptamer-functionalized cationic liposome for synergistic anti-breast cancer effects in vivo. J Biomed Nanotechnol. 2019;15:1135–48. [DOI]

49.

Guerra F, Arbini AA, Moro L. Mitochondria and cancer chemoresistance. Biochim Biophys Acta Bioenerg. 2017;1858:686–99. [DOI]

50.

Guaragnella N, Giannattasio S, Moro L. Mitochondrial dysfunction in cancer chemoresistance. Biochem Pharmacol. 2014;92:62–72. [DOI]

51.

Farge T, Saland E, De Toni F, Aroua N, Hosseini M, Perry R, et al. Chemotherapy-resistant human acute myeloid leukemia cells are not enriched for leukemic stem cells but require oxidative metabolism. Cancer Discov. 2017;7:716–35. [DOI] [PubMed] [PMC]

52.

De Luca A, Fiorillo M, Peiris-Pagès M, Ozsvari B, Smith DL, Sanchez-Alvarez R, et al. Mitochondrial biogenesis is required for the anchorage-independent survival and propagation of stem-like cancer cells. Oncotarget. 2015;6:14777–95. [DOI] [PubMed] [PMC]

53.

Jiang L, Li L, He X, Yi Q, He B, Cao J, et al. Overcoming drug-resistant lung cancer by paclitaxel loaded dual-functional liposomes with mitochondria targeting and pH-response. Biomaterials. 2015;52:126–39. [DOI]

54.

Chen H, Tian J, Liu D, He W, Guo Z. Dual aptamer modified dendrigraft poly-L-lysine nanoparticles for overcoming multi-drug resistance through mitochondrial targeting. J Mater Chem B. 2017;5:972–9. [DOI] [PubMed]

55.

Itoh M, Kitano T, Watanabe M, Kondo T, Yabu T, Taguchi Y, et al. Possible role of ceramide as an indicator of chemoresistance: decrease of the ceramide content via activation of glucosylceramide synthase and sphingomyelin synthase in chemoresistant leukemia. Clin Cancer Res. 2003;9:415–23. [PubMed]

56.

van Vlerken LE, Duan Z, Seiden MV, Amiji MM. Modulation of intracellular ceramide using polymeric nanoparticles to overcome multidrug resistance in cancer. Cancer Res. 2007;67:4843–50. [DOI]

57.

Devalapally H, Duan Z, Seiden MV, Amiji MM. Modulation of drug resistance in ovarian adenocarcinoma by enhancing intracellular ceramide using tamoxifen-loaded biodegradable polymeric nanoparticles. Clin Cancer Res. 2008;14:3193–203. [DOI]

58.

Shete HK, Prabhu RH, Patravale VB. Endosomal escape: a bottleneck in intracellular delivery. J Nanosci Nanotechnol. 2014;14:460–74. [DOI]

59.

Kedmi R, Veiga N, Ramishetti S, Goldsmith M, Rosenblum D, Dammes N, et al. A modular platform for targeted RNAi therapeutics. Nat Nanotechnol. 2018;13:214–9. [DOI]

60.

Shah SA, Khan MA, Arshad M, Awan S, Hashmi M, Ahmad N. Doxorubicin-loaded photosensitive magnetic liposomes for multi-modal cancer therapy. Colloids Surf B Biointerfaces. 2016;148:157–64. [DOI]

61.

Sun T, Zhang YS, Pang B, Hyun DC, Yang M, Xia Y. Engineered nanoparticles for drug delivery in cancer therapy. Angew Chem Int Ed Engl. 2014;53:12320–64. [DOI]

62.

He H, Zhou J, Liu Y, Liu S, Xie Z, Yu M, et al. Near-infrared-light-induced morphology transition of poly (ether amine) nanoparticles for supersensitive drug release. ACS Appl Mater Interfaces. 2018;10:7413–21. [DOI]

63.

Nittayacharn P, Yuan HX, Hernandez C, Bielecki P, Zhou H, Exner AA. Enhancing tumor drug distribution with ultrasound-triggered nanobubbles. J Pharm Sci. 2019;108:3091–8. [DOI]

64.

Zhou C, Xie X, Yang H, Zhang S, Li Y, Kuang C, et al. Novel class of ultrasound-triggerable drug delivery systems for the improved treatment of tumors. Mol Pharm. 2019;16:2956–65. [DOI]

65.

Göpferich A. Mechanisms of polymer degradation and erosion. Biomaterials. 1996;17:103–14. [DOI]

66.

Lin SY, Chen KS, Teng HH, Li MJ. In vitro degradation and dissolution behaviours of microspheres prepared by three low molecular weight polyesters. J Microencapsul. 2000;17:577–86. [DOI]

67.

Panyam J, Labhasetwar V. Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv Drug Deliv Rev. 2003;55:329–47. [DOI]

68.

Lucke A, Kiermaier J, Gopferich A. Peptide acylation by poly(alpha-hydroxy esters). Pharm Res. 2002;19:175–81. [DOI]

69.

Weiss VM, Lucas H, Mueller T, Chytil P, Etrych T, Naolou T, et al. Intended and unintended targeting of polymeric nanocarriers: the case of modified poly (glycerol adipate) nanoparticles. Macromol Biosci. 2018;18:1700240. [DOI]

70.

Grossen P, Witzigmann D, Sieber S, Huwyler J. PEG-PCL-based nanomedicines: a biodegradable drug delivery system and its application. J Control Release. 2017;260:46–60. [DOI]

71.

Swainson SME, Taresco V, Pearce AK, Clapp LH, Ager B, McAllister M, et al. Exploring the enzymatic degradation of poly(glycerol adipate). Eur J Pharm Biopharm. 2019;142:377–86. [DOI]

72.

Qi C, Lin J, Fu LH, Huang P. Calcium-based biomaterials for diagnosis, treatment, and theranostics. Chem Soc Rev. 2018;47:357–403. [DOI]

73.

Yao X, Mu J, Zeng L, Lin J, Nie Z, Jiang X, et al. Stimuli-responsive cyclodextrin-based nanoplatforms for cancer treatment and theranostics. Mater Horiz. 2019;6:846–70. [DOI]

74.

Li JL. Dual drug delivery system based on biodegradable organosilica core-shell architectures. ACS Appl Mater Interfaces. 2018;10:5287–95. [DOI]

75.

Mu J, Lin J, Huang P, Chen X. Development of endogenous enzyme-responsive nanomaterials for theranostics. Chem Soc Rev. 2018;47:5554–73. [DOI]

76.

Fu LH, Qi C, Lin J, Huang P. Catalytic chemistry of glucose oxidase in cancer diagnosis and treatment. Chem Soc Rev. 2018;47:6454–72. [DOI]

77.

Wang S, Huang P, Chen X. Stimuli-responsive programmed specific targeting in nanomedicine. ACS Nano. 2016;10:2991–4. [DOI]

78.

Wang S, Huang P, Chen X. Hierarchical targeting strategy for enhanced tumor tissue accumulation/retention and cellular internalization. Adv Mater. 2016;28:7340–64. [DOI]

79.

Ju Y, Tong S, Hou Y. Stimuli-regulated cancer theranostics based on magnetic nanoparticles. In: Clin Appl Magnetic Nanoparticles. 1st ed. New York: CRC Press; 2018.p.22. [DOI]

80.

Bansal A, Zhang Y. Photocontrolled nanoparticle delivery systems for biomedical applications. Acc Chem Res. 2014;47:3052–60. [DOI]

81.

Fan W, Yung B, Huang P, Chen X. Nanotechnology for multimodal synergistic cancer therapy. Chem Rev. 2017;117:13566–638. [DOI]

82.

Li Q, Li W, Di H, Luo L, Zhu C, Yang J, et al. A photosensitive liposome with NIR light triggered doxorubicin release as a combined photodynamic-chemo therapy system. J Control Release. 2018;277:114–25. [DOI]

83.

Zhang Y, Wan Y, Chen Y, Blum NT, Lin J, Huang P. Ultrasound-enhanced chemo-photodynamic combination therapy by using albumin “nanoglue”-based nanotheranostics. ACS Nano. 2020;14:5560–9. [DOI]

84.

Zanganeh S, Spitler R, Hutter G, Ho JQ, Pauliah M, Mahmoudi M. Tumor-associated macrophages, nanomedicine and imaging: the axis of success in the future of cancer immunotherapy. Immunotherapy. 2017;9:819–35. [DOI] [PubMed]

85.

Zeelen C, Paus C, Draper D, Heskamp S, Signore A, Galli F, et al. In vivo imaging of tumor-infiltrating immune cells: implications for cancer immunotherapy. Q J Nucl Med Mol Imaging. 2018;62:56–77. [DOI] [PubMed]

86.

Yang C, Blum NT, Lin J, Qu J, Huang P. Biomaterial scaffold-based local drug delivery systems for cancer immunotherapy. Science Bulletin. 2020;65:1489–504. [DOI]

87.

Jia Y, Omri A, Krishnan L, McCluskie MJ. Potential applications of nanoparticles in cancer immunotherapy. Hum Vaccin Immunother. 2017;13:63–74. [DOI]

88.

Schluck M, Hammink R, Figdor CG, Verdoes M, Weiden J. Biomaterial-based activation and expansion of tumor-specific T cells. Front Immunol. 2019;10:931. [DOI] [PubMed] [PMC]

89.

Mandal S, Eksteen-Akeroyd ZH, Jacobs MJ, Hammink R, Koepf M, Lambeck AJ, et al. Therapeutic nanoworms: towards novel synthetic dendritic cells for immunotherapy. Chem Sci. 2013;4:4168–74. [DOI]

90.

Dolmans DE, Fukumura D, Jain RK. Photodynamic therapy for cancer. Nat Rev Cancer. 2003;3:380–7. [DOI] [PubMed]

91.

Nakajima Takahito T. Improving the efficacy of Photoimmunotherapy (PIT) using a cocktail of antibody conjugates in a multiple antigen tumor model. Theranostics. 2013;3:357–65. [DOI] [PubMed] [PMC]

92.

Nagaya T, Nakamura Y, Sato K, Zhang YF, Ni M, Choyke PL, et al. Near infrared photoimmunotherapy with an anti-mesothelin antibody. Oncotarget. 2016;7:23361–9. [DOI] [PubMed] [PMC]

93.

Watanabe R, Hanaoka H, Sato K, Nagaya T, Harada T, Mitsunaga M, et al. Photoimmunotherapy targeting prostate-specific membrane antigen: are antibody fragments as effective as antibodies? J Nucl Med. 2015;56:140–4. [DOI] [PubMed] [PMC]

94.

Nishimura T, Mitsunaga M, Ito K, Kobayashi H, Saruta M. Cancer neovasculature-targeted near-infrared photoimmunotherapy (NIR-PIT) for gastric cancer: different mechanisms of phototoxicity compared to cell membrane-targeted NIR-PIT. Gastric Cancer. 2020;23:82–94. [DOI]

95.

Cognetti D, Curry J, Gillenwater A, William W, Kochuparambil S, McDonald D, et al. A phase 2a, multicenter, open-label study of RM-1929 photoimmunotherapy in patients with recurrent head and neck cancer. Int J Radiat Oncol. 2018;100:1368. [DOI]

96.

Ogawa M, Tomita Y, Nakamura Y, Lee MJ, Lee S, Tomita S, et al. Immunogenic cancer cell death selectively induced by near infrared photoimmunotherapy initiates host tumor immunity. Oncotarget. 2017;8:10425–36. [DOI] [PubMed] [PMC]

97.

Nakajima K, Takakura H, Shimizu Y, Ogawa M. Changes in plasma membrane damage inducing cell death after treatment with near-infrared photoimmunotherapy. Cancer Sci. 2018;109:2889–96. [DOI]

98.

Xia Y, Tian J, Chen X. Effect of surface properties on liposomal siRNA delivery. Biomaterials. 2016;79:56–68. [DOI]

99.

Hatakeyama H, Akita H, Harashima H. A multifunctional envelope type nano device (MEND) for gene delivery to tumours based on the EPR effect: a strategy for overcoming the PEG dilemma. Adv Drug Deliv Rev. 2011;63:152–60. [DOI]

100.

Fang Y, Xue J, Gao S, Lu A, Yang D, Jiang H, et al. Cleavable PEGylation: a strategy for overcoming the “PEG dilemma” in efficient drug delivery. Drug Deliv. 2017;24:22–32. [DOI]

101.

Shi J, Kantoff PW, Wooster R, Farokhzad OC. Cancer nanomedicine: progress, challenges and opportunities. Nat Rev Cancer. 2017;17:20–37. [DOI]

102.

Walkey CD, Olsen JB, Guo H, Emili A, Chan WC. Nanoparticle size and surface chemistry determine serum protein adsorption and macrophage uptake. J Am Chem Soc. 2012;134:2139–47. [DOI]

103.

Badkas A, Frank E, Zhou Z, Jafari M, Chandra H, Sriram V, et al. Modulation of in vitro phagocytic uptake and immunogenicity potential of modified Herceptin®-conjugated PLGA-PEG nanoparticles for drug delivery. Colloids Surf B Biointerfaces. 2018;162:271–8. [DOI]

104.

Bhattacharjee Sourav S. DLS and zeta potential-what they are and what they are not? J Control Release. 2016;235:337–51. [DOI] [PubMed]

105.

Danhier F. To exploit the tumor microenvironment: since the EPR effect fails in the clinic, what is the future of nanomedicine? J Control Release. 2016;244:108–21. [DOI] [PubMed]

106.

Maeda Hiroshi H. Toward a full understanding of the EPR effect in primary and metastatic tumors as well as issues related to its heterogeneity. Adv Drug Deliv Rev. 2015;91:3–6. [DOI]

107.

Zhang B, Hu Y. Modulating the tumor microenvironment to enhance tumor nanomedicine delivery. Front Pharmacol. 2017;8:952. [DOI]

108.

Griffon-Etienne G, Boucher Y, Brekken C, Suit HD, Jain RK. Taxane-induced apoptosis decompresses blood vessels and lowers interstitial fluid pressure in solid tumors: clinical implications. Cancer Res. 1999;59:3776–82. [PubMed]

109.

Danhier F, Danhier P, Magotteaux N, De Preter G, Ucakar B, Karroum O, et al. Electron paramagnetic resonance highlights that the oxygen effect contributes to the radiosensitizing effect of paclitaxel. PLoS One. 2012;7:e40772. [DOI] [PubMed] [PMC]

110.

Taghian AG, Abi-Raad R, Assaad SI, Casty A, Ancukiewicz M, Yeh E, et al. Paclitaxel decreases the interstitial fluid pressure and improves oxygenation in breast cancers in patients treated with neoadjuvant chemotherapy: clinical implications. J Clin Oncol. 2005;23:1951–61. [DOI]

111.

Seki T, Fang J, Maeda H. Enhanced delivery of macromolecular antitumor drugs to tumors by nitroglycerin application. Cancer Sci. 2009;100:2426–30. [DOI]

112.

Cabral H, Matsumoto Y, Mizuno K, Chen Q, Murakami M, Kimura M, et al. Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size. Nat Nanotechnol. 2011;6:815–23. [DOI] [PubMed]

113.

Noble GT, Stefanick JF, Ashley JD, Kiziltepe T, Bilgicer B. Ligand-targeted liposome design: challenges and fundamental considerations. Trends Biotechnol. 2014;32:32–45. [DOI]

114.

Voltan AR, Alarcon KM, Fusco-Almeida AM, Soares CP, Mendes-Giannini MJ, Chorilli M. Highlights in Endocytosis of Nanostructured Systems. Curr Med Chem. 2017;24:1909–29. [DOI]

115.

Bazak R, Houri M, El Achy S, Kamel S, Refaat T. Cancer active targeting by nanoparticles: a comprehensive review of literature. J Cancer Res Clin Oncol. 2015;141:769–84. [DOI]

116.

Ramasamy T, Ruttala HB, Gupta B, Poudel BK, Choi HG, Yong CS, et al. Smart chemistry-based nanosized drug delivery systems for systemic applications: a comprehensive review. J Control Release. 2017;258:226–53. [DOI]

117.

Tran S, DeGiovanni PJ, Piel B, Rai P. Cancer nanomedicine: a review of recent success in drug delivery. Clin Transl Med. 2017;6:44. [DOI] [PubMed] [PMC]

118.

Zhang YS, Zhang YN, Zhang W. Cancer-on-a-chip systems at the frontier of nanomedicine. Drug Discov Today. 2017;22:1392–9. [DOI]

119.

Bhise NS, Ribas J, Manoharan V, Zhang YS, Polini A, Massa S, et al. Organ-on-a-chip platforms for studying drug delivery systems. J Control Release. 2014;190:82–93. [DOI]

120.

Gharagozloo M, Majewski S, Foldvari M. Therapeutic applications of nanomedicine in autoimmune diseases: from immunosuppression to tolerance induction. Nanomedicine. 2015;11:1003–18. [DOI]

121.

Feng X, Liu J, Xu W, Li G, Ding J. Tackling autoimmunity with nanomedicines. Nanomedicine. 2020; 15:1585–97. [DOI]

122.

Brusini R, Varna M, Couvreur P. Advanced nanomedicines for the treatment of inflammatory diseases. Adv Drug Deliv Rev. 2020;157:161–78. [DOI]

123.

Xie A, Hanif S, Ouyang J, Tang Z, Kong N, Kim NY, et al. Stimuli-responsive prodrug-based cancer nanomedicine. EBioMedicine. 2020;56:102821. [DOI]

124.

Ling X, Tu J, Wang J, Shajii A, Kong N, Feng C, et al. Glutathione-responsive prodrug nanoparticles for effective drug delivery and cancer therapy. ACS Nano. 2019;13:357–70. [DOI]

125.

Sun B, Luo C, Yu H, Zhang X, Chen Q, Yang W, et al. Disulfide bond-driven oxidation- and reduction-responsive prodrug nanoassemblies for cancer therapy. Nano Lett. 2018;18:3643–50. [DOI]

126.

Dai Y, Xiao H, Liu J, Yuan Q, Ma Pa, Yang D, et al. In vivo multimodality imaging and cancer therapy by near-infrared light-triggered trans-platinum pro-drug-conjugated upconverison nanoparticles. J Am Chem Soc. 2013;135:18920–9. [DOI]