Abstract
Conventional anticancer drugs display significant shortcomings which limit their use in cancer therapy. For this reason, important progress has been achieved in the field of nanotechnology to solve these problems and offer a promising and effective alternative for cancer treatment. Nanoparticle drug delivery systems exploit the abnormal characteristics of tumour tissues to selectively target their payloads to cancer cells, either by passive, active or triggered targeting. Additionally, nanoparticles can be easily tuned to improve their properties, thereby increasing the therapeutic index of the drug. Liposomes, polymeric nanoparticles, polymeric micelles and polymer- or lipid-drug conjugate nanoparticles incorporating cytotoxic therapeutics have been developed; some of them are already on the market and others are under clinical and preclinical research. However, there is still much research to be done to be able to defeat the limitations of traditional anticancer therapy. This review focuses on the potential of nanoparticle delivery systems in cancer treatment and the current advances achieved.
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References
World Health Organization (2011) Cancer. Fact Sheet #297
Luo J, Solimini NL, Elledge SJ (2009) Principles of cancer therapy: oncogene and non-oncogene addiction. Cell 136:823–837
Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70
Park JH, von Maltzahn G, Xu MJ et al (2010) Cooperative nanomaterial system to sensitize, target, and treat tumors. Proc Natl Acad Sci U S A 107:981–986
Sahoo SK, Parveen S, Panda JJ (2007) The present and future of nanotechnology in human health care. Nanomedicine 3:20–31
Sahoo SK, Labhasetwar V (2003) Nanotech approaches to drug delivery and imaging. Drug Discov Today 8:1112–1120
Shaffer C (2005) Nanomedicine transforms drug delivery. Drug Discov Today 10:1581–1582
Moghimi SM, Hunter AC, Murray JC (2005) Nanomedicine: current status and future prospects. FASEB J 19:311–330
Davis ME, Chen ZG, Shin DM (2008) Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat Rev Drug Discov 7:771–782
Allen TM, Cullis PR (2004) Drug delivery systems: entering the mainstream. Science 303:1818–1822
Bae KH, Chung HJ, Park TG (2011) Nanomaterials for cancer therapy and imaging. Mol Cells 31:295–302
Panyam J, Labhasetwar V (2003) Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv Drug Deliv Rev 55:329–347
Kohandel M, Kardar M, Milosevic M, Sivaloganathan S (2007) Dynamics of tumor growth and combination of anti-angiogenic and cytotoxic therapies. Phys Med Biol 52:3665–3677
Maeda H, Wu J, Sawa T et al (2000) Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release 65:271–284
Jain RK, Stylianopoulos T (2010) Delivering nanomedicine to solid tumors. Nat Rev Clin Oncol 7:653–664
Padera TP, Kadambi A, di Tomaso E et al (2002) Lymphatic metastasis in the absence of functional intratumor lymphatics. Science 296:1883–1886
Maeda H (2001) The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting. Adv Enzyme Regul 41:189–207
Cho K, Wang X, Nie S et al (2008) Therapeutic nanoparticles for drug delivery in cancer. Clin Cancer Res 14:1310–1316
Pelicano H, Martin DS, Xu RH, Huang P (2006) Glycolysis inhibition for anticancer treatment. Oncogene 25:4633–4646
Liechty WB, Caldorera-Moore M, Phillips MA et al (2011) Advanced molecular design of biopolymers for transmucosal and intracellular delivery of chemotherapeutic agents and biological therapeutics. J Control Release 155:119–127
Bae YH, Park K (2011) Targeted drug delivery to tumors: myths, reality and possibility. J Control Release 153:198–205
Torchilin VP (2010) Passive and active drug targeting: drug delivery to tumors as an example. Handb Exp Pharmacol (197):3–53
Byrne JD, Betancourt T, Brannon-Peppas L (2008) Active targeting schemes for nanoparticle systems in cancer therapeutics. Adv Drug Deliv Rev 60:1615–1626
Parveen S, Misra R, Sahoo SK (2011) Nanoparticles: a boon to drug delivery, therapeutics, diagnostics and imaging. Nanomedicine (in press)
Lammers T, Kiessling F, Hennink WE, Storm G (2011) Drug targeting to tumors: principles, pitfalls and (pre-) clinical progress. J Control Release (in press)
Tagami T, Ernsting MJ, Li SD (2011) Optimization of a novel and improved thermosensitive liposome formulated with DPPC and a Brij surfactant using a robust in vitro system. J Control Release 154:290–297
Tagami T, Ernsting MJ, Li SD (2011) Efficient tumor regression by a single and low dose treatment with a novel and enhanced formulation of thermosensitive liposomal doxorubicin. J Control Release 152:303–309
Alexis F, Pridgen E, Molnar LK, Farokhzad OC (2008) Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol Pharm 5:505–515
Kazuo M (2011) Intracellular targeting delivery of liposomal drugs to solid tumors based on EPR effects. Adv Drug Deliv Rev 63:161–169
Owens DE 3rd, Peppas NA (2006) Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm 307:93–102
Gratton SE, Ropp PA, Pohlhaus PD et al (2008) The effect of particle design on cellular internalization pathways. Proc Natl Acad Sci U S A 105: 11613–11618
Bangham AD, Horne RW (1964) Negative staining of phospholipids and their structural modification by surface-active agents as observed in the electron microscope. J Mol Biol 8:660–668
Sapra P, Allen TM (2003) Ligand-targeted liposomal anticancer drugs. Prog Lipid Res 42:439–462
Hofheinz RD, Gnad-Vogt SU, Beyer U, Hochhaus A (2005) Liposomal encapsulated anti-cancer drugs. Anticancer Drugs 16:691–707
Singal PK, Iliskovic N (1998) Doxorubicin-induced cardiomyopathy. N Engl J Med 339:900–905
Gaitanis A, Staal S (2010) Liposomal doxorubicin and nab-paclitaxel: nanoparticle cancer chemotherapy in current clinical use. Methods Mol Biol 624:385–392
Keller AM, Mennel RG, Georgoulias VA et al (2004) Randomized phase III trial of pegylated liposomal doxorubicin versus vinorelbine or mitomycin C plus vinblastine in women with taxanerefractory advanced breast cancer. J Clin Oncol 22:3893–3901
O’Brien MER, Wigler N, Inbar M et al (2004) 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 15:440–449
Northfelt DW, Dezube BJ, Thommes JA et al (1998) Pegylated-liposomal doxorubicin versus doxorubicin, bleomycin, and vincristine in the treatment of AIDS-related Kaposi’s sarcoma: results of a randomized phase III clinical trial. J Clin Oncol 16:2445–2451
Gordon AN, Fleagle JT, Guthrie D et al (2001) Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol 19:3312–3322
Sparano JA, Makhson AN, Semiglazov VF et al (2009) Pegylated liposomal doxorubicin plus docetaxel significantly improves time to progression without additive cardiotoxicity compared with docetaxel monotherapy in patients with ad vanced breast cancer previously treated with neoadjuvantadjuvant anthracycline therapy: results from a randomized phase III study. J Clin Oncol 27:4522–4529
Orlowski RZ, Nagler A, Sonneveld P et al (2007) Randomized phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma: combination therapy improves time to progression. J Clin Oncol 25:3892–3901
Davies Cde L, Lundstrom LM, Frengen J et al (2004) Radiation improves the distribution and uptake of liposomal doxorubicin (caelyx) in human osteosarcoma xenografts. Cancer Res 64:547–553
Harris L, Batist G, Belt R et al; TLC D-99 Study Group (2002) Liposome-encapsulated doxorubicin compared with conventional doxorubicin in a randomized multicenter trial as first-line therapy of metastatic breast carcinoma. Cancer 94:25–36
Batist G, Ramakrishnan G, Rao CS et al (2001) Reduced cardiotoxicity and preserved antitumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized, multicenter trial of metastatic breast cancer. J Clin Oncol 19:1444–1454
Gill PS, Wernz J, Scadden DT et al (1996) Randomized phase III trial of liposomal daunorubicin versus doxorubicin, bleomycin, and vincristine in AIDS-related Kaposi’s sarcoma. J Clin Oncol 14:2353–2364
Stathopoulos GP, Boulikas T (2012) Lipoplatin formulation review article. J Drug Deliv 581363–581372
Zamboni WC, Ramalingam S, Friedland DM et al (2009) Phase I and pharmacokinetic study of pegylated liposomal CKD-602 in patients with advanced malignancies. Clin Cancer Res 15:1466–1472
Batist G, Gelmon KA, Chi KN et al (2009) Safety, pharmacokinetics, and efficacy of CPX-1 liposome injection in patients with advanced solid tumors. Clin Cancer Res 15:692–700
Sankhala KK (2009) A phase I pharmacokinetic (PK) study of MBP-426, a novel liposome encapsulated oxaliplatin. J Clin Oncol 27:2535
Matsumura Y, Gotoh M, Muro K et al (2004) Phase I and pharmacokinetic study of MCC-465, a doxorubicin (DXR) encapsulated in PEG immunoliposome, in patients with metastatic stomach cancer. Ann Oncol 15:517–525
Wang X, Wang Y, Chen ZG, Shin DM (2009) Advances of cancer therapy by nanotechnology. Cancer Res Treat 41:1–11
Miele E, Spinelli GP, Miele E et al (2009) Albumin-bound formulation of paclitaxel (Abraxane ABI-007) in the treatment of breast cancer. Int J Nanomed 4:99–105
Crown J, O’Leary M (2000) The taxanes: an update. Lancet 355:1176–1178
Rowinsky EK, Eisenhauer EA, Chaudhry V et al (1993) Clinical toxicities encountered with paclitaxel (Taxol). Semin Oncol 20:1–15
Gradishar WJ, Tjulandin S, Davidson N et al (2005) Phase III trial of nanoparticle albuminbound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol 23:7794–7803
Roy V, LaPlant BR, Gross GG et al; North Central Cancer Treatment Group (2009) Phase II trial of weekly nab (nanoparticle albumin-bound)-paclitaxel (nab-paclitaxel) (Abraxane) in combination with gemcitabine in patients with metastatic breast cancer (N0531). Ann Oncol 20:449–453
Lobo C, Lopes G, Baez O et al (2010) Final results of a phase II study of nab-paclitaxel, bevacizumab, and gemcitabine as first-line therapy for patients with HER2-negative metastatic breast cancer. Breast Cancer Res Treat 123:427–435
Svenson S, Wolfgang M, Hwang J et al (2011) Preclinical to clinical development of the novel camptothecin nanopharmaceutical CRLX101. J Control Release 153:49–55
Davis ME (2009) The first targeted delivery of siRNA in humans via a self-assembling, cyclodextrin polymer-based nanoparticle: from concept to clinic. Mol Pharm 6:659–668
Ozpolat B, Sood AK, Lopez-Berestein G (2010) Nanomedicine based approaches for the delivery of siRNA in cancer. J Intern Med 267:44–53
Whitehead KA, Langer R, Anderson DG (2009) Knocking down barriers: advances in siRNA delivery. Nat Rev Drug Discov 8:129–138
Bawarski WE, Chidlowsky E, Bharali DJ, Mousa SA (2008) Emerging nanopharmaceuticals. Nanomedicine 4:273–282
Kim DW, Kim SY, Kim HK et al (2007) Multicenter phase II trial of Genexol-PM, a novel Cremophor-free, polymeric micelle formulation of paclitaxel, with cisplatin in patients with advanced non-small-cell lung cancer. Ann Oncol 18:2009–2014
Lee KS, Chung HC, Im SA et al (2008) Multicenter phase II trial of Genexol-PM, a Cremophorfree, polymeric micelle formulation of paclitaxel, in patients with metastatic breast cancer. Breast Cancer Res Treat 108:241–250
Kim HJ, Kim KH, Yun J et al (2011) Phase II clinical trial of Genexol(R) (paclitaxel) and carboplatin for patients with advanced non-small cell lung cancer. Cancer Res Treat 43:19–23
Matsumura Y, Hamaguchi T, Ura T et al (2004) Phase I clinical trial and pharmacokinetic evaluation of NK911, a micelle-encapsulated doxorubicin. Br J Cancer 91:1775–1781
Kato K, Chin K, Yoshikawa T et al (2011) Phase II study of NK105, a paclitaxel-incorporating micellar nanoparticle, for previously treated advanced or recurrent gastric cancer. Invest New Drugs (in press)
Plummer R, Wilson RH, Calvert H et al (2011) A Phase I clinical study of cisplatin-incorporated polymeric micelles (NC-6004) in patients with solid tumours. Br J Cancer 104:593–598
Hamaguchi T, Doi T, Eguchi-Nakajima T et al (2010) Phase I study of NK012, a novel SN-38-incorporating micellar nanoparticle, in adult patients with solid tumors. Clin Cancer Res 16:5058–5066
Valle JW, Armstrong A, Newman C et al (2011) A phase 2 study of SP1049C, doxorubicin in P-glycoprotein-targeting pluronics, in patients with advanced adenocarcinoma of the esophagus and gastroesophageal junction. Invest New Drugs 29:1029–1037
Vasey PA, Kaye SB, Morrison R et al (1999) Phase I clinical and pharmacokinetic study of PK1 [N-(2-hydroxypropyl)methacrylamide copolymer doxorubicin]: first member of a new class of chemotherapeutic agents-drug-polymer conjugates. Clin Cancer Res 5:83–94
Rademaker-Lakhai JM, Terret C, Howell SB et al (2004) A Phase I and pharmacological study of the platinum polymer AP5280 given as an intravenous infusion once every 3 weeks in patients with solid tumors. Clin Cancer Res 10:3386–3395
Nowotnik DP, Cvitkovic E (2009) ProLindac™ (AP5346): a review of the development of an HPMA DACH platinum polymer therapeutic. Adv Drug Deliv Rev 61:1214–1219
Sabbatini P, Aghajanian C, Dizon D et al (2004) Phase II study of CT-2103 in patients with recurrent epithelial ovarian, Fallopian tube, or primary peritoneal carcinoma. J Clin Oncol 22:4523–4531
Homsi J, Simon GR, Garrett CR et al (2007) Phase I trial of poly-L-glutamate camptothecin (CT-2106) administered weekly in patients with advanced solid malignancies. Clin Cancer Res 13:5855–5861
Bigioni M, Parlani M, Bressan A et al (2009) Antitumor activity of delimotecan against human metastatic melanoma: pharmacokinetics and molecular determinants. Int J Cancer 125:2456–2464
Veltkamp SA, Witteveen EO, Capriati A et al (2008) Clinical and pharmacologic study of the novel prodrug delimotecan (MEN 4901/T-0128) in patients with solid tumors. Clin Cancer Res 14:7535–7544
Danhauser-Riedl S, Hausmann E, Schick HD et al (1993) Phase I clinical and pharmacokinetic trial of dextran conjugated doxorubicin (AD-70, DOXOXD). Invest New Drugs 11:187–195
Bolling C, Graefe T, Lübbing C et al (2006) Phase II study of MTX-HSA in combination with Cisplatin as first line treatment in patients with advanced or metastatic transitional cell carcinoma. Invest New Drugs 24:521–527
Aleku M, Schulz P, Keil O et al (2008) Atu027, a liposomal small interfering RNA formulation targeting protein kinase N3, inhibits cancer progression. Cancer Res 68:9788–9798
Chawla SP, Chua VS, Fernandez L et al (2010) Advanced phase I/II studies of targeted gene delivery in vivo: intravenous Rexin-G for gemcitabineresistant metastatic pancreatic cancer. Mol Ther 18:435–441
Prakash S, Malhotra M, Shao W et al (2011) Polymeric nanohybrids and functionalized carbon nanotubes as drug delivery carriers for cancer therapy. Adv Drug Deliv Rev 63:1340–1351
Cheng Y, Zhao L, Li Y, Xu T (2011) Design of biocompatible dendrimers for cancer diagnosis and therapy: current status and future perspectives. Chem Soc Rev 40:2673–2703
Estella-Hermoso de Mendoza A, Campanero MA, Mollinedo F, Blanco-Prieto MJ (2009) Lipid nanomedicines for anticancer drug therapy. J Biomed Nanotechnol 5:323–343
Dhar S, Kolishetti N, Lippard SJ, Farokhzad OC (2011) Targeted delivery of a cisplatin prodrug for safer and more effective prostate cancer therapy in vivo. Proc Natl Acad Sci U S A 108:1850–1855
Battaglia L, Serpe L, Muntoni E et al (2011) Methotrexate-loaded SLNs prepared by coacervation technique: in vitro cytotoxicity and in vivo pharmacokinetics and biodistribution. Nanomedicine (Lond) 6:1561–1573
Ding D, Zhu Z, Liu Q et al (2011) Cisplatin-loaded gelatin-poly(acrylic acid) nanoparticles: synthesis, antitumor efficiency in vivo and penetration in tumors. Eur J Pharm Biopharm 79:142–149
Parhi P, Mohanty C, Sahoo SK (2011) Enhanced cellular uptake and in vivo pharmacokinetics of rapamycin-loaded cubic phase nanoparticles for cancer therapy. Acta Biomater 7:3656–3669
Jain A, Jain SK, Ganesh N et al (2010) Design and development of ligand-appended polysaccharidic nanoparticles for the delivery of oxaliplatin in colorectal cancer. Nanomedicine 6:179–190
Lammers T, Peschke P, Kühnlein R et al (2007) Effect of radiotherapy and hyperthermia on the tumor accumulation of HPMA copolymer-based drug delivery systems. J Control Release 117:333–341
Lammers T, Subr V, Ulbrich K et al (2010) Polymeric nanomedicines for image-guided drug delivery and tumor-targeted combination therapy. Nano Today 5:197–212
Yang X, Dou S, Sun T et al (2011) Systemic delivery of siRNA with cationic lipid assisted PEGPLA nanoparticles for cancer therapy. J Control Release 156:203–211
Duan J, Zhang Y, Han S et al (2010) Synthesis and in vitro/in vivo anti-cancer evaluation of curcumin-loaded chitosan/poly(butyl cyanoacrylate) nanoparticles. Int J Pharm 400:211–220
Oh KS, Song JY, Cho SH et al (2010) Paclitaxelloaded Pluronic nanoparticles formed by a temperature-induced phase transition for cancer therapy. J Control Release 148:344–350
Zhu Z, Li Y, Li X et al (2010) Paclitaxel-loaded poly(N-vinylpyrrolidone)-b-poly(ɛ-caprolactone) nanoparticles: preparation and antitumor activity in vivo. J Control Release 142:438–446
Kim J, Kim Y, Park K et al (2008) Antitumor efficacy of cisplatin-loaded glycol chitosan nanoparticles in tumor-bearing mice. J Control Release 127:41–49
Zhang W, Shi Y, Chen Y et al (2010) Enhanced antitumor efficacy by Paclitaxel-loaded Pluronic P123/F127 mixed micelles against non-small cell lung cancer based on passive tumor targeting and modulation of drug resistance. Eur J Pharm Biopharm 75:341–353
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Egusquiaguirre, S.P., Igartua, M., Hernández, R.M. et al. Nanoparticle delivery systems for cancer therapy: advances in clinical and preclinical research. Clin Transl Oncol 14, 83–93 (2012). https://doi.org/10.1007/s12094-012-0766-6
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DOI: https://doi.org/10.1007/s12094-012-0766-6