In Situ Generated Gold Nanoparticle Hybrid Polymersomes for Water‐Soluble Chemotherapeutics: Inhibited Leakage and pH‐Responsive Intracellular Release

Abstract

to liposomes, but with enhanced stability and more tunable functionalization. Since methoxy-poly(ethylene glycol)-b-polylactide vesicles were created, [5] polymersomes have played tremendously active roles as promising carriers for water-soluble drugs in the application of cancer therapy. Regarding drug release behavior, it is generally expected that polymersomes ought to hold as much cargo as possible in the circulatory system for a few hours or longer until they reach cancer tissue via enhanced permeability and retention effect. To date, a number of studies have been focused on how to trigger drug release out of polymersomes after uptake by cancer cells. Based on this concept, various smart vesicles to accelerate intracellular drug release, responsive to microenvironmental changes of cancers such as pH, [6] redox, [7] enzyme, [8] or ambient physical stimulus, [9] have been developed. In contrast, how to ensure drug retention of polymersomes in the bloodstream was investigated much less, except some strategies related to cross-linking hydrophobic membrane containing methacrylate or butadiene by photoirradiation or chemical reactions. [10,11] Actually, premature drug release in the circulation is quite serious, which has become a common problem for polymersomes, particularly those loaded with watersoluble drugs. As reported in 2010, [12] a biodegradable chimeric polymersome of asymmetric poly(ethylene glycol)-b-poly(εcaprolactone)-b-poly(2-(diethylamino) ethyl methacrylate) copolymers was prepared to encapsulate FITC-cytochrome C, but the burst release behavior was so obvious that the cumulative FITCcytochrome C release was ≈60% in 10 h at pH 7.4. As another example, [13] when encapsulated into α-carboxyl poly(ethylene glycol)-b-poly(d,l-lactide) polymersomes, 6-carboxyfluorescein showed an initial rapid release followed by a gradual decrease. In the first 2 min, 30% 6-carboxyfluorescein was released. Moreover, in the case of vesicles comprising block copolymers between poly(γ-benzyl l-glutamate) and hyaluronan, [14] results indicated a sudden doxorubicin hydrochloride (DOX·HCl) release of ≈50% at 24 h. These cases remind us that it is of great importance to overcome this critical problem of drug leakage from polymersomes, otherwise it would impair anticancer efficacy and aggravate side effects of chemotherapeutics.Drug leakage in blood circulation is generally a serious concern to polymersomes when loading water-soluble chemotherapeutics. If packing density of polymersome membrane is strengthened, premature drug release will be inhibited. Therefore, synthesis of a series of amphiphilic polyphosphazenes (PNPs) with 2-diethylaminoethyl 4-aminobenzoate (DEAB) as hydrophobic side groups and amino-terminal poly(ethylene glycol) (NH 2 -PEG 2000 ) as hydrophilic chains is presented. By controlling the ratio of DEAB to NH 2 -PEG 2000 , the optimal PNP-3 is screened to ensure polymersome formation and high loading of doxorubicin hydrochloride (DOX·HCl). In situ generation method is initially employed to introduce gold na...

Hybrid Vesicular Drug Delivery Systems for Cancer Therapeutics

“…Gold nanoparticles were homogenously distributed among DEAB moieties and acted as inorganic cross‐links to aggregate polymeric chains ( Figure ). The results of the study indicated that not only did the drug accumulation in the tumor tissue increase in mice, but also that the pH‐responsive capability of the particles led to fast intracellular action while drug leakage at pH 7.4 was dramatically reduced …”

“…Schematic image summarizing the method to incorporate gold nanoparticles into PNP nanoparticles and the intracellular release of the cargo due to the pH‐sensitive properties of the nanoparticle. Adapted with permission . Copyright 2017, Wiley.…”

Recent Advances in Amphiphilic Polymers as the Stabilizers of Colloidal Gold Nanoparticles

“…Cavallaro and co‐workers prepared amphiphilic graft polymer containing amine and thiol groups for anchoring AuNPs to obtain a positive surface for siRNA delivery . Qiu and co‐workers prepared amphiphilic graft polymer with 2‐diethylaminoethyl 4‐aminobenzoate as hydrophobic pendant groups and PEG as hydrophilic chains for vesicle formation and high loading of DOX, as shown in Figure . AuNPs were in situ generated and homogeneously distributed in the polymer via coordination interaction as inorganic crosslinkers.…”

“…Amphiphilic graft polymer for loading anticancer drug to form the vesicles, which hybridize AuNPs via coordination interaction to prolong the systemic circulation time of the vesicles. Reproduced with permission . Copyright 2017, WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.…”

“…[69] Qiu and co-workers prepared amphiphilic graft polymer with 2-diethylaminoethyl 4-aminobenzoate as hydrophobic pendant groups and PEG as hydrophilic chains for vesicle formation and high loading of DOX, as shown in Figure 6. [70] AuNPs were in situ generated…”