Long Circulating Self-Assembled Nanoparticles from Cholesterol-Containing Brush-Like Block Copolymers for Improved Drug Delivery to Tumors

Abstract

Amphiphilic brush-like block copolymers composed of polynorbonene-cholesterol/poly(ethylene glycol) (P(NBCh9-b-NBPEG)) self-assembled to form a long circulating nanostructure capable of encapsulating the anticancer drug doxorubicin (DOX) with high drug loading (22.1% w/w). The release of DOX from the DOX-loaded P(NBCh9-b-NBPEG) nanoparticles (DOX-NPs) was steady at less than 2% per day in PBS. DOX-NPs were effectively internalized by human cervical cancer cells (HeLa) and showed dose-dependent cytotoxicity, whereas blank nanoparticles were noncytotoxic. The DOX-NPs demonstrated a superior in vivo circulation time relative to that of free DOX. Tissue distribution and in vivo imaging studies showed that DOX-NPs preferentially accumulated in tumor tissue with markedly reduced accumulation in the heart and other vital organs. The DOX-NPs greatly improved survival and significantly inhibited tumor growth in tumor-bearing SCID mice compared to that for the untreated and free DOX-treated groups. The results indicated that self-assembled P(NBCh9-b-NBPEG) may be a useful carrier for improving tumor delivery of hydrophobic anticancer drugs.

Possible role of nanocarriers in drug delivery against cervical cancer

“…Bleomycin sulfate-loaded nanostructured lipid particles resulted in improved oral bioavailability by avoiding first-pass metabolism and thereby upsurges in intestinal lymphatic uptake of drug to reach systemic circulation, finally leading to greater toxicity and apoptosis against cervical cancer cells [54]. Doxorubicin-encapsulated long circulating self-assembled nanoparticles prepared using amphiphilic brush-like block copolymer composed of polynorbonene-cholesterol/poly(ethylene glycol) were found to display considerably greater inhibition of tumor growth as compared with free doxorubicin and it was concluded that the prepared nanoparticles would be a valuable carrier for improving tumor drug delivery [55]. Confocal laser scanning microscopy (CLSM) revealed that doxorubicin hydrochloride-loaded pH-responsive charge reversal, polymer-coated mesoporous silica nanoparticles resulted in effective delivery and release of doxorubicin hydrocholride to the nucleus of HeLa cells [56].…”

“…No.DrugType/composition of nanoparticlesCell lines/animal models/neoplasmReferences1.DocetaxelPoly( ɛ -caprolactoneco-lactide)-D-α-tocopheryl polyethylene glycol succinate nanoparticlesCervical cancer cells[50]2.DocetaxelColic acid-PLGA-b-Vitamin E TPGS copolymer–[51]3.CisplatinFolic acid-conjugated gelatin nanoparticles–[52]4.–Phenanthridinium (oligonucleotide intercalator)-functionalized mesoporous silica nanoparticlesHeLa cells[53]5.Bleomycin sulfateNanostructured lipid particlesCervical cancer cells[54]6.DoxorubicinPolynorbonene-cholesterol/poly(ethylene glycol)–[55]7.DoxorubicinMesoporous silica nanoparticlesHeLa cells[56]8.DocetaxelD-α-tocopheryl polyethylene glycol 1000 succinate-b-poly(ε-caprolactone-ran-lactide) nanoparticlesXenograft BALB/c nude mice tumor model[57]9.DoxorubicinCyclodextrin-containing pH-sensitive poly(2-(dimethylamino) ethyl methacrylate) star polymer nanoparticles–[58]10.PaclitaxelPoly(γ-glutamic acid-maleimide-co-l-lactide)-1,2-dipalmitoylsn-glycero-3-phosphoethanolamine (γ-PGA-MAL-PLADPPE) copolymer-based nanoparticles–[59]11.DocetaxelPoly(lactide-co-glycolide) and pluronic F68C...…”

A novel paclitaxel-loaded poly(D,L-lactide-co-glycolide)-Tween 80 copolymer nanoparticle overcoming multidrug resistance for lung cancer treatment

“…14 In addition, NPs could be controlled to release the drug gradually and effectively, and prolong the circulation half-life of drug in plasma, which demonstrates that the application of NPs in anticancer drug delivery systems shows superiority over the conventional chemotherapy. 15 NPs, made of natural or synthetic macromolecules, have been extensively explored by scientists. [16][17][18][19] The unique physical properties allow them to be used as imaging probes to locate and identify cancerous lesions.…”

Redox-sensitive nanoparticles from amphiphilic cholesterol-based block copolymers for enhanced tumor intracellular release of doxorubicin

“…26-30 Our previous studies have shown that amphiphilic brush block copolymers containing cholesterol blocks formed long circulating self-assembled nanoparticles for improved DOX delivery to tumor. 31, 32 However, these nanoparticles showed a very slow drug release pattern that reduced their anti-tumor effect. 32 …”

“…31, 32 However, these nanoparticles showed a very slow drug release pattern that reduced their anti-tumor effect. 32 …”