Polymeric micelles: Basic research to clinical practice.

Owing to the complex and still not fully understood physiological environment, the development of traditional nanosized drug delivery systems is very challenging for precision cancer therapy. It is very difficult to control the in vivo distribution of nanoparticles after intravenous injection. The ideal drug nanocarriers should not only have stealth surface for prolonged circulation time but also possess enhanced cellular internalization in tumor sites. Unfortunately, the stealth surface and enhanced cellular uptake seem contradictory to each other. How to integrate the two opposite aspects into one system is a very herculean but meaningful task. As an alternative drug delivery strategy, chameleon-like drug delivery systems were developed to achieve long circulation time while maintaining enhanced cancer cell uptake. Such drug nanocarriers can "turn off" their internalization ability during circulation. However, the enhanced cellular uptake can be readily activated upon arriving at tumor tissues. In this way, stealth surface and enhanced uptake are of dialectical unity in drug delivery. In this review, we focus on the surface engineering of drug nanocarriers to obtain simultaneous stealth surfaces in circulation and enhanced uptake in tumors. The current strategies and ongoing developments, including programmed tumor-targeting strategies and some specific zwitterionic surfaces, will be discussed in detail.

Rational Design of Cancer Nanomedicine for Simultaneous Stealth Surface and Enhanced Cellular Uptake.

Fluorescent materials have recently received great attention in biomedical research because of their good optical properties, species diversity and high sensitivity. However, most of the traditional fluorophores suffer from the aggregation-caused quenching (ACQ) effect at high concentration or in the aggregated state, which has greatly limited their biomedical applications. Fluorescent materials with the AIE effect show exactly the opposite effect to the ACQ effect, and have exhibited significant advantages in terms of tunable emission, excellent photostability and biocompatibility. In this review, we summarize current advances of AIE-based materials for biomedical applications. In particular, AIE-active biosensors for detecting biomolecules, such as hydrogen peroxide, hydrogen sulfide, biothiols and enzymes, have been summarized. Moreover, AIE-based materials applied for bioimaging, drug delivery and cancer theranostics have also been described in detail. In the last section, the future prospects and possible challenges in the development of AIE-based materials are discussed briefly.

Advances in luminescent materials with aggregation-induced emission (AIE) properties for biomedical applications.

Well-defined A3(BC)3 type amphiphilic miktoarm star polymers poly(e-caprolactone)3-[poly(2-(diethylamino)ethyl methacrylate)-b-poly(poly(ethylene glycol) methyl ether methacrylate)]3 [(PCL)3-(PDEAEMA-b-PPEGMA)3] and their pH-sensitive self-assembled polymeric micelles were developed as anticancer vehicles for improved cancer therapy. These miktoarm star polymers were synthesized by a combination of ring opening polymerization (ROP) and continuous activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) and characterized by GPC and 1H NMR measurement. The CMC values of the miktoarm star polymers in aqueous solution were extremely low (0.0029–0.0035 mg mL−1), suggesting that the micelles are relatively stable in solution. The self-assembled blank and doxorubicin (DOX)-loaded micelles were spherical in morphology with average sizes of 110–240 nm depending on the architecture of the copolymers, which were determined by transmission electron microscopy (TEM) and dynamic light scattering (DLS). When decreasing pH from 7.4 to 5.0, the micelles underwent globule–uneven–extended conformational transitions, and in vitro drug release rates were significantly accelerated, owing to the swelling of micelles at lower pH conditions caused by the protonation of tertiary amine groups of DEAEMA. Moreover, the drug release profiles at different pH values were well fitted by a semi-empirical equation. The in vitro cytotoxicity of DOX-loaded micelles against HepG2 cells suggested that DOX-loaded (PCL)3-(PDEAEMA-b-PPEGMA)3 micelles exhibited similar anti-tumor activities to free DOX, with at least 80% decrease in cell viability after 48 h incubation. Intracellular uptake demonstrated that DOX was delivered into the cells effectively after the cells were incubated with DOX-loaded micelles. The results demonstrated that the pH-responsive (PCL)3-(PDEAEMA-b-PPEGMA)3 micelles could be used as latent vehicles for delivering hydrophobic anticancer drugs with controlled and sustained release behavior.

Amphiphilic miktoarm star copolymer (PCL)3-(PDEAEMA-b-PPEGMA)3 as pH-sensitive micelles in the delivery of anticancer drug.

A biomimic pH-sensitive polymeric prodrug based on polycarbonate for intracellular drug delivery

pH-responsive and biodegradable polymeric micelles based on poly(β-amino ester)-graft-phosphorylcholine for doxorubicin delivery

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pH-responsive and biodegradable polymeric micelles based on poly(β-amino ester)-graft-phosphorylcholine for doxorubicin delivery