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...