The Use of Nanocarriers for Drug Delivery in Cancer Therapy

The use of nanocarriers as drug delivery systems for chemotherapeutic agents can improve the overall pharmacological properties of commonly used drugs in chemotherapy. The clinical success, as well as the ease with which surface modifi cations can be made to both liposomes and micelles to accommodate targeting ligands have made these nanocarriers in particular attractive candidates for future work involving targeted drug delivery. Although not targeted, there are clinically approved liposomal-based drugs that are currently used to treat various types of cancers. Furthermore, there are several other formulations involving both of these nanocarriers which are now in various stages of clinical trials. This review discusses the use of liposomes and micelles in cancer therapy and attempts to provide some current information regarding the clinical status of several of these nanocarrier-based drugs. In addition, recent work involving the incorporation of targeting ligands to systems such as these in order to improve colocalization between the drug and cancer cells is also addressed. Furthermore, while the use of these nanocarriers in particular is the primary focus here, this review also contains a discussion on other commonly used nanocarriers in cancer therapy to include various polymer-based and polymer-protein conjugates. Finally, the possibility of using combinatorial approaches involving multiple surface modifi cations made to both liposomes and micelles in order to further improve their drug delivery capabilities is also discussed.

[1]  R. Bukowski,et al.  Treating cancer with PEG Intron , 2002, Cancer.

[2]  Ruth Duncan,et al.  Polymer conjugates as anticancer nanomedicines , 2006, Nature Reviews Cancer.

[3]  M. Fishman,et al.  Final results of a phase I study of liposome encapsulated SN-38 (LE-SN38): Safety, pharmacogenomics, pharmacokinetics, and tumor response , 2005 .

[4]  P. Keegan,et al.  FDA drug approval summary: pegaspargase (oncaspar) for the first-line treatment of children with acute lymphoblastic leukemia (ALL). , 2007, The oncologist.

[5]  G. Fields,et al.  Effects of Drug Hydrophobicity on Liposomal Stability , 2007, Chemical biology & drug design.

[6]  H. Tajiri,et al.  Target chemotherapy of anti-CD147 antibody-labeled liposome encapsulated GSH-DXR conjugate on CD147 highly expressed carcinoma cells. , 2009, International journal of oncology.

[7]  F. Foss.  Interleukin‐2 Fusion Toxin: Targeted Therapy for Cutaneous T Cell Lymphoma , 2001, Annals of the New York Academy of Sciences.

[8]  V. Torchilin,et al.  Liposomes A practical approach Second Edition , 2003 .

[9]  V. Torchilin,et al.  Polymeric micelles for delivery of poorly soluble drugs: Preparation and anticancer activity in vitro of paclitaxel incorporated into mixed micelles based on poly(ethylene glycol)-lipid conjugate and positively charged lipids , 2005, Journal of drug targeting.

[10]  A. Gabizon.  Stealth liposomes and tumor targeting: one step further in the quest for the magic bullet. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[11]  Liposomal anthracyclines in metastatic breast cancer: clinical update. , 2003, The oncologist.

[12]  F. Szoka,et al.  Liposome-encapsulated doxorubicin targeted to CD44: a strategy to kill CD44-overexpressing tumor cells. , 2001, Cancer research.

[13]  F. Foss,et al.  DAB(389)IL-2 (ONTAK): a novel fusion toxin therapy for lymphoma. , 2000, Clinical lymphoma.

[14]  D. Kerr,et al.  Phase I dose escalation and pharmacokinetic study of pluronic polymer-bound doxorubicin (SP1049C) in patients with advanced cancer , 2004, British Journal of Cancer.

[15]  T. Secomb,et al.  Two-mechanism peak concentration model for cellular pharmacodynamics of Doxorubicin. , 2005, Neoplasia.

[16]  M. Ranson,et al.  A phase 2 study of SP1049C, doxorubicin in P-glycoprotein-targeting pluronics, in patients with advanced adenocarcinoma of the esophagus and gastroesophageal junction , 2011, Investigational New Drugs.

[17]  Vladimir P. Torchilin,et al.  Immunomicelles: Targeted pharmaceutical carriers for poorly soluble drugs , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[18]  R. Tu,et al.  Peptide-mediated targeting of liposomes to tumor cells. , 2007, Methods in molecular biology.

[19]  S. Hirohashi,et al.  Transarterial Chemotherapy with Zinostatin Stimalamer for Hepatocellular Carcinoma , 1998, Oncology.

[20]  F. Szoka,et al.  Chemical approaches to triggerable lipid vesicles for drug and gene delivery. , 2003, Accounts of chemical research.

[21]  L. Gerweck,et al.  Tumor pH controls the in vivo efficacy of weak acid and base chemotherapeutics , 2006, Molecular Cancer Therapeutics.

[22]  Y. Nagasaki,et al.  Sugar-installed block copolymer micelles: their preparation and specific interaction with lectin molecules. , 2001, Biomacromolecules.

[23]  R. New,et al.  Liposomes : a practical approach , 1990 .

[24]  K. Kogure,et al.  [Development of a novel systemic gene delivery system for cancer therapy with a tumor-specific cleavable PEG-lipid]. , 2007, Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan.

[25]  H Akita,et al.  Development of a novel systemic gene delivery system for cancer therapy with a tumor-specific cleavable PEG-lipid , 2007, Gene Therapy.

[26]  Vladimir P. Torchilin,et al.  Enhanced in vivo antitumor efficacy of poorly soluble PDT agent, meso-tetraphenylporphine, in PEG-PE-based tumor-targeted immunomicelles , 2007, Cancer biology & therapy.

[27]  F. Bates,et al.  Polymer vesicles in vivo: correlations with PEG molecular weight. , 2003, Journal of controlled release : official journal of the Controlled Release Society.

[28]  Eun Seong Lee,et al.  Doxorubicin-loaded polymeric micelle overcomes multidrug resistance of cancer by double-targeting folate receptor and early endosomal pH. , 2008, Small.

[29]  V. Torchilin.  Targeted pharmaceutical nanocarriers for cancer therapy and imaging , 2007, The AAPS Journal.

[30]  A. Gabizon.  Pegylated Liposomal Doxorubicin: Metamorphosis of an Old Drug into a New Form of Chemotherapy , 2001, Cancer investigation.

[31]  H. Ueno,et al.  A phase I and pharmacokinetic study of NK105, a paclitaxel-incorporating micellar nanoparticle formulation , 2007, British Journal of Cancer.

[32]  R. Langer,et al.  Synthesis and characterization of dextran-peptide-methotrexate conjugates for tumor targeting via mediation by matrix metalloproteinase II and matrix metalloproteinase IX. , 2004, Bioconjugate chemistry.

[33]  S. Armes,et al.  in vitro biological evaluation of folate-functionalized block copolymer micelles for selective anti-cancer drug delivery. , 2008, Macromolecular bioscience.

[34]  D. Kerr,et al.  Phase II studies of polymer-doxorubicin (PK1, FCE28068) in the treatment of breast, lung and colorectal cancer. , 2009, International journal of oncology.

[35]  T. Chiou,et al.  Vincristine-induced dysphagia suggesting esophageal motor dysfunction: a case report. , 2000, Japanese journal of clinical oncology.

[36]  M. Backer,et al.  Adapter protein for site-specific conjugation of payloads for targeted drug delivery. , 2004, Bioconjugate chemistry.

[37]  T. Park,et al.  Hyaluronic acid-paclitaxel conjugate micelles: synthesis, characterization, and antitumor activity. , 2008, Bioconjugate chemistry.

[38]  Xu Wang,et al.  Application of Nanotechnology in Cancer Therapy and Imaging , 2008, CA: a cancer journal for clinicians.

[39]  E. Miele,et al.  Albumin-bound formulation of paclitaxel (Abraxane® ABI-007) in the treatment of breast cancer , 2009, International journal of nanomedicine.

[40]  C. Cerveny,et al.  Novel antitumor prodrugs designed for activation by matrix metalloproteinases-2 and -9. , 2004, Molecular pharmaceutics.

[41]  Ghaleb A Husseini,et al.  Micelles and nanoparticles for ultrasonic drug and gene delivery. , 2008, Advanced drug delivery reviews.

[42]  Alexander V Kabanov,et al.  Polymer genomics: an insight into pharmacology and toxicology of nanomedicines. , 2006, Advanced drug delivery reviews.

[43]  D. Siwak,et al.  The potential of drug-carrying immunoliposomes as anticancer agents. Commentary re: J. W. Park et al., Anti-HER2 immunoliposomes: enhanced efficacy due to targeted delivery. Clin. Cancer Res., 8: 1172-1181, 2002. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[44]  He Zhang,et al.  Tumor-targeted PE38KDEL delivery via PEGylated anti-HER2 immunoliposomes. , 2009, International journal of pharmaceutics.

[45]  A. Boddy,et al.  Phase I and pharmacokinetic study of NC-6004, a new platinum entity of cisplatin-conjugated polymer forming micelles , 2008 .

[46]  Nevin Celebi,et al.  Controlled delivery of peptides and proteins. , 2007, Current pharmaceutical design.

[47]  I. Tannock,et al.  Inhibition of endosomal sequestration of basic anticancer drugs: influence on cytotoxicity and tissue penetration , 2006, British Journal of Cancer.

[48]  K. Garber.  For Bexxar, FDA meeting offers long-awaited chance at approval. , 2002, Journal of the National Cancer Institute.

[49]  J. Fréchet,et al.  pH-Responsive copolymer assemblies for controlled release of doxorubicin. , 2005, Bioconjugate chemistry.

[50]  G. Fields,et al.  Targeted drug delivery utilizing protein-like molecular architecture. , 2007, Journal of the American Chemical Society.

[51]  Q. Ping,et al.  Targeted delivery of doxorubicin using stealth liposomes modified with transferrin. , 2009, International journal of pharmaceutics.

[52]  H. Maeda,et al.  Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[53]  P. Ghezzi,et al.  Protective Effect of Erythropoietin and Its Carbamylated Derivative in Experimental Cisplatin Peripheral Neurotoxicity , 2006, Clinical Cancer Research.

[54]  Jinming Gao,et al.  Multifunctional Micellar Nanomedicine for Cancer Therapy , 2009, Experimental biology and medicine.

[55]  Y. Shimada,et al.  Phase I and pharmacokinetic study of MCC-465, a doxorubicin (DXR) encapsulated in PEG immunoliposome, in patients with metastatic stomach cancer. , 2004, Annals of oncology : official journal of the European Society for Medical Oncology.

[56]  K. Gelmon,et al.  Safety, Pharmacokinetics, and Efficacy of CPX-1 Liposome Injection in Patients with Advanced Solid Tumors , 2009, Clinical Cancer Research.

[57]  N. Russian,et al.  THE POTENTIAL OF DRUG-CARRYING IMMUNOLIPOSOMES AS ANTICANCER AGENTS , 2008 .

[58]  P. Cullis,et al.  Drug Delivery Systems: Entering the Mainstream , 2004, Science.

[59]  N. Agarwal,et al.  Obesity and Treatment of Prostate Cancer: What Is the Right Dose of Lupron Depot? , 2007, Clinical Cancer Research.