Traditional chemotherapy suffers from severe toxicity and side effects that limit its maximum application in cancer therapy. To overcome this challenge, an ideal treatment strategy would be to selectively control the release or regulate the activity of drugs to minimize the undesirable toxicity. Recently, ultrasound (US)‐responsive drug delivery systems (DDSs) have attracted significant attention due to the non‐invasiveness, high tissue penetration depth, and spatiotemporal controllability of US. Moreover, the US‐induced mechanical force has been proven to be a robust method to site‐selectively rearrange or cleave bonds in mechanochemistry. This review describes the US‐activated DDSs from the fundamental basics and aims to present a comprehensive summary of the current understanding of US‐responsive DDSs for controlled drug release and drug activation. First, we summarize the typical mechanisms for US‐responsive drug release and drug activation. Second, the main factors affecting the ultrasonic responsiveness of drug carriers are outlined. Furthermore, representative examples of US‐controlled drug release and drug activation are discussed, emphasizing their novelty and design principles. Finally, the challenges and an outlook on this promising therapeutic strategy are discussed.

Rational design of controllable drug release systems is important for tumor treatments due to the nonspecific toxicity of many chemotherapeutics. Herein, laser or light responsive pharmaceutical delivery nanoparticles are designed, by taking the advantages of redox responsive selenium (Se) substituted polymer as shell and photosensitive porphyrin zirconium metal–organic frameworks (MOF) as core. In detail, redox cleavable di‐(1‐hydroxylundecyl) selenide (DH‐Se), biocompatible poly(ethylene glycol) (PEG), and poly(propylene glycol) (PPG) are randomly polymerized to form poly(DH‐Se/PEG/PPG urethane), which is used to coat the reactive oxygen species' (ROS) producible porous porphyrin zirconium metal organization formulation (PCN‐224 MOF) to form the final poly(DH‐Se/PEG/PPG urethane)@MOF shell–core nanoparticle with spherical shape by emulsion approach. Interestingly, poly(DH‐Se/PEG/PPG urethane)@MOF nanoparticles with loading of chemotherapeutic doxorubicin (DOX) experience a fast and controllable release, which can realize the combination of chemotherapy and photodynamic therapy upon irradiation with laser light, due to the light‐triggered ROS production by MOF which further causes the cleavage of poly(DH‐Se/PEG/PPG urethane) polymer chain and the release of encapsulated DOX. To the best of the authors' knowledge, this is the first design of utilizing MOF and selenium substituted polymer as controllable drug release carriers, which might be beneficial for precise chemotherapy and photodynamic therapy combination.

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Although the gelation process and lower critical solution temperature (LCST) behavior are well acknowledged in polymer systems, low-molecular-weight gelators (LMWGs) rarely display LCST behavior during supramolecular gelation. Herein, we report an LMWG system with LCST-type thermoresponsiveness and an LCST-triggered supramolecular gelation process. Temperature plays a crucial role in this system, not only affecting the LCST phase separation but also triggering the gelation process. The backbones (three-dimensional structures) of the resulting hydrogel are the hierarchical assemblies of the LMWG undergoing the LCST phase separation. Hence, the gelation of the LMWG is only realized when the gelation temperature is above the critical transition temperature (T cloud) of the LCST behavior, which is different from many supramolecular or polymeric hydrogel systems.

Promising applications of poly[(R)-3-hydroxybutyrate-(R)-3-hydroxyhexanoate] (PHBHx) in tissue engineering have been extensively investigated. However, the application of PHBHx in drug delivery has been rarely explored due to its hydrophobic property, limited functionality, and the absence of active groups for reaction. In this work, PHBHx has been functionalized and copolymerized with poly(ethylene glycol) (PEG) and polypropylene glycol (PPG) oligomers to provide a series of novel PHBHx incorporated polyurethanes (PHxEP). In vitro docetaxel (DTX) release showed that DTX loaded thermogel can achieve sustained, zero-order release of DTX, that is, constant 10% release of the payload up to 10 days, which is unique and different from other systems previously reported. The inhibition effect of DTX loaded thermogel on solid tumors was evaluated using mouse tumor models, and its biosafety was evaluated. DTX-loaded thermogel showed enhanced antimelanoma effect on melanoma solid tumors compared to the free DTX drug and no apparent harm to other tissues including liver, heart, spleen, kidney, and lung tissues. The results indicated that the PHxEP-based thermogel can be a hopeful drug delivery candidate for sustained and constant delivery of anticancer drugs. It is the first time that the functionalized PHBHx-based water-soluble thermogels have been reported as the drug carrier for DTX release.

In recent years, naturally biodegradable polyhydroxyalkanoate (PHA) monopolymers have become focus of public attentions due to their good biocompatibility. However, due to its poor mechanical properties, high production costs, and limited functionality, its applications in materials, energy, and biomedical applications are greatly limited. In recent years, researchers have found that PHA copolymers have better thermal properties, mechanical processability, and physicochemical properties relative to their homopolymers. This review summarizes the synthesis of PHA copolymers by the latest biosynthetic and chemical modification methods. The modified PHA copolymer could greatly reduce the production cost with elevated mechanical or physicochemical properties, which can further meet the practical needs of various fields. This review further summarizes the broad applications of modified PHA copolymers in biomedical applications, which might shred lights on their commercial applications.

Aqueous chitosan-based polymer solution formed thermogel upon injection to accelerate the recovery of oral mucosa-related ulcers with desired properties.