Biofunctionalized polymer-lipid supported mesoporous silica nanoparticles for release of chemotherapeutics in multidrug resistant cancer cells.
Multidrug resistance (MDR) is a major impediment to the success of cancer chemotherapy. A polymer-lipid supported mesoporous silica nanoparticle (PLS-MSNs) is described here to facilitate intracellular delivery of anticancer drug and enhance the antitumor efficacy against MDR breast cancer cells. By coating MSNs with a synthetic dual-functional polymer-lipid material P123-DOPE, the supported membrane acted as an intact barrier against the escape of encapsulated drugs before reaching the target cells, leading to depolymerization and triggered storm release of loaded irinotecan (CPT-11) in acidic endosomal pH of tumor cells. In addition, P123-DOPE can inhibit breast cancer resistance protein (BCPR) mediated CPT-11 efflux in drug resistant MCF-7/BCRP breast cancer cells, thus acting as a "door blocker". Compared to free CPT-11, PLS-MSNs resulted in a maximum increase in the intracellular CPT-11 concentration (12.9-fold), had 7.1-fold higher cytotoxicity and processed a stronger cell cycle arrest in MCF-7/BCRP cells. Moreover, CPT-11 loaded PLS-MSNs showed high therapeutic performance and low toxicity in BALB/c nude mice bearing drug resistant breast tumors, with an inhibition rate of 81.2% compared to free CPT-11 treatment group. The reported PLS-MSNs provide promising applicability in future preclinical and clinical MDR cancer treatment.
Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai, China.
Xinxin
X
Zhang
Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai, China.
Feifei
F
Li
Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai, China.
Shiyan
S
Guo
School of Pharmaceutics, China Pharmaceutical University, Nanjing, China.
Xi
X
Chen
Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai, China.
Xiaoli
X
Wang
School of Pharmaceutics, China Pharmaceutical University, Nanjing, China. Electronic address: lijuancpu@163.com.
Juan
J
Li
Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai, China. Electronic address: simm2122@vip.sina.com.
Yong
Y
Gan
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002166:Camptothecin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D000077146:Irinotecan; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009363:Neoplasm Proteins / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*; D055672:Static Electricity; D013997:Time Factors; D014961:X-Ray Diffraction; D023041:Xenograft Model Antitumor Assays
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D008055:Lipids; D009363:Neoplasm Proteins; D011108:Polymers; D012822:Silicon Dioxide; D000077146:Irinotecan; D000255:Adenosine Triphosphate; D002166:Camptothecin
Breast cancer resistance protein; Irinotecan; Mesoporous silica nanoparticle; Multidrug resistance; Triggered release