A biodegradable triblock copolymer, poly(ethylene oxide)-block-poly(allyl glycidyl ether)-block-poly(DL-lactide) (mPEG-b-PAGE-b-PLA), with allyl groups on its middle block was designed and synthesized through anionic polymerization of allyl glycidyl ether (AGE) with PEG monomethyl ether sodium salt as the macroinitiator and subsequent ring-opening polymerization of DL-lactide. Luteinizing hormone-releasing hormone (LHRH) was conjugated to the PAGE block through a linkage of –SCH2CH2C(O)NH– between the allyl and LHRH residues. The LHRH content in the conjugate was ca. 25 wt%. Owing to the amphiphilic nature of the conjugate, it was self-assembled into micelles of 15–40 nm in diameter and with the LHRH moieties in the hydrophilic corona of the micelles. Cellular uptake experiments were carried out using flow cytometry and confocal laser scanning microscopy (CLSM) with HeLa cells as LHRH-receptor overexpressing cells and HepG-2 cells as normal cells. HeLa cells displayed more cellular uptake of the LHRH-micelles than the normal cells. In vivo biodistribution of the LHRH-containing micelles and LHRH-free micelles was studied using a CRI Maestro™ imaging system. Preferred accumulation in tumor sites of LHRH-containing micelles was observed at 24 hours post injection. Therefore, LHRH-conjugated amphiphilic copolymers might be used as a potential drug delivery system for the treatment of LHRH receptor overexpressing carcinoma.

A dinuclear Pt(II) complex, di-DACH-Pt(II), was synthesized, characterized, and then tethered to a biodegradable and amphiphilic copolymer, and a polymer based dinuclear platinum(II) complex micelle, M(di-DACH-Pt), was prepared. The micelles showed reduced systemic toxicity and enhanced antitumor efficacy.

A biodegradable and amphiphilic copolymer, poly(ethylene glycol)-block-poly(l-lactide-co-2-methyl-2-carboxyl-propylene carbonate) (mPEG-b-P(LA-co-MCC)), which contains pendant carboxyl groups, was chosen as a drug carrier for the active anticancer part (diaminocyclohexane platinum, DACH-Pt) of oxaliplatin to form mPEG-b-P(LA-co-MCC/Pt) complex. A folic acid-conjugated copolymer, folic acid–poly(ethylene glycol)-block-poly(l-lactide) (FA–PEG-PLA), with similar chemical structure was chosen for targeting. Multifunctional micelles were successfully prepared by a coassembling method. In vitro evaluation was performed by using SKOV-3 and MCF-7 cancer cells. In vivo blood clearance of platinum was studied, and the results show that micelles exhibit longer blood circulation after iv injection. Pt biodistribution was studied by measuring its levels in plasma, organs, and tumors, especially in tumor cell DNA, by atomic absorption and inductively coupled plasma mass spectrometry. Antitumor activity was assessed in mice bearing H22 liver cancers, and the results showed that the micelles with FA moieties exhibited greater antitumor efficacy than those without FA or oxaliplatin. Therefore, these novel multifunctional platinum micelles have great potential in future clinical application.Keywords: biodegradable; folic acid targeting; multifunctional micelles; oxaliplatin; polymer−platinum complex;

A biodegradable triblock copolymer, poly(ethylene oxide)-block-poly(allyl glycidyl ether)-block-poly(DL-lactide) (mPEG-b-PAGE-b-PLA), with allyl groups on its middle block was designed and synthesized through anionic polymerization of allyl glycidyl ether (AGE) with PEG monomethyl ether sodium salt as the macroinitiator and subsequent ring-opening polymerization of DL-lactide. Luteinizing hormone-releasing hormone (LHRH) was conjugated to the PAGE block through a linkage of –SCH2CH2C(O)NH– between the allyl and LHRH residues. The LHRH content in the conjugate was ca. 25 wt%. Owing to the amphiphilic nature of the conjugate, it was self-assembled into micelles of 15–40 nm in diameter and with the LHRH moieties in the hydrophilic corona of the micelles. Cellular uptake experiments were carried out using flow cytometry and confocal laser scanning microscopy (CLSM) with HeLa cells as LHRH-receptor overexpressing cells and HepG-2 cells as normal cells. HeLa cells displayed more cellular uptake of the LHRH-micelles than the normal cells. In vivo biodistribution of the LHRH-containing micelles and LHRH-free micelles was studied using a CRI Maestro™ imaging system. Preferred accumulation in tumor sites of LHRH-containing micelles was observed at 24 hours post injection. Therefore, LHRH-conjugated amphiphilic copolymers might be used as a potential drug delivery system for the treatment of LHRH receptor overexpressing carcinoma.

A dinuclear Pt(II) complex, di-DACH-Pt(II), was synthesized, characterized, and then tethered to a biodegradable and amphiphilic copolymer, and a polymer based dinuclear platinum(II) complex micelle, M(di-DACH-Pt), was prepared. The micelles showed reduced systemic toxicity and enhanced antitumor efficacy.