Design of an Injectable Polypeptide Hydrogel Depot Containing the Immune Checkpoint Blocker Anti-PD-L1 and Doxorubicin to Enhance Antitumor Combination Therapy.

Combination therapy can be used to enhance the therapeutic response and decrease side effects during cancer treatment. In this study, a system is developed to locally deliver the immune checkpoint blockade antibody targeting programmed death-ligand 1 (anti-PD-L1 or aPD-L1) and doxorubicin (Dox), by an injectable, biocompatible polypeptide hydrogel as a drug depot. The localized and sustained release of Dox after the intratumoral injection of the co-loaded hydrogel induces immunogenic tumor cell death, thus promoting an antitumor immunological response. The tumor inhibitory effect is significantly enhanced by the simultaneous release of aPD-L1 at the tumor site thanks to its action on the inhibition of the PD-1/PD-L1 pathway and restoration of the tumor-killing effect of cytotoxic T cells. Treatment of the B16F10 melanoma model with the aPD-L1 and Dox co-loaded hydrogel leads to a remarkable inhibition of tumor progression and prolongation of animal survival.

Room temperature preparation of fluorescent starch nanoparticles from starch-dopamine conjugates and their biological applications.

Fluorescent organic nanoparticles (FONs) have been regarded as the promising candidates for biomedical applications owing to their well adjustment of chemical structure and optical properties and good biological properties. However, the preparation of FONs from the natural derived polymers has been rarely reported thus far. In current work, we reported a novel strategy for preparation of FONs based on the self-polymerization of starch-dopamine conjugates and polyethyleneimine in rather mild experimental conditions, including air atmosphere, aqueous solution, absent catalysts and at room temperature. The morphology, chemical structure and optical properties of the resultant starch-based FONs were investigated by different characterization techniques. Biological evaluation results demonstrated that these starch-based FONs possess good biocompatibility and fluorescent imaging performance. More importantly, the novel strategy might also be extended for the preparation of many other carbohydrate polymers based FONs with different structure and functions. Therefore, this work opens a new avenue for the preparation and biomedical applications of luminescent carbohydrate polymers.

Biomimetic PEGylation of carbon nanotubes through surface-initiated RAFT polymerization.

Carbon nanotubes (CNTs) are a type of one-dimensional carbon nanomaterials that possess excellent physicochemical properties and have been potentially utilized for a variety of applications. Surface modification of CNTs with polymers is a general route to expand and improve the performance of CNTs and has attracted great research interest over the past few decades. Although many methods have been developed previously, most of these methods still showed some disadvantages, such as low efficiency, complex experimental procedure and harsh reaction conditions etc. In this work, we reported a practical and novel way to fabricate CNTs based polymer composites via the combination of mussel inspired chemistry and reversible addition fragmentation chain transfer (RAFT) polymerization. First, the amino group was introduced onto the surface of CNTs via self-polymerization of dopamine. Then, chain transfer agent can be immobilized on the amino groups functionalized CNTs to obtain CNT-PDA-CTA, which can be utilized for surface-initiated RAFT polymerization. A water soluble and biocompatible monomer poly(ethylene glycol) monomethyl ether methacrylate (PEGMA) was adopted to fabricate pPEGMA functionalized CNTs through RAFT polymerization. The successful preparation of CNTs based polymer composites (CNT-pPEGMA) was confirmed by transmission electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis and X-ray photoelectron spectroscopy in details. The CNT-pPEGMA showed good dispersibility and desirable biocompatibility, making them highly potential for biomedical applications. More importantly, a large number of CNTs based polymer composites could also be fabricated through the same strategy when different monomers were used due to the good monomer adaptability of RAFT polymerization. Therefore, this strategy should be a general method for preparation of various multifunctional CNTs based polymer composites.

The one-step acetalization reaction for construction of hyperbranched and biodegradable luminescent polymeric nanoparticles with aggregation-induced emission feature.

The development of luminescent bioprobes based on organic dyes with aggregation-induced emission (AIE) characteristic has attracted great attention in recent years. In this work, we reported for the first time that AIE-active luminescent polymeric nanoparticles (LPNs) can be facilely prepared via a one-step acetalization reaction, which can be used to conjugate the aldehyde group containing AIE dye (PTH-CHO) and methoxypolyethylene glycols (mPEG-CHO) with a commercially available dendritic polyester (H40) using p-toluenesulfonic acid (TsOH) as the catalyst. As-prepared star-shaped hyperbranched luminescent polymers (named as H40-mPEG-mPTH) were prone to self-assemble into core-shell nanoparticles in aqueous solution because of their amphiphilic structure, in which hydrophobic components (such as PTH-CHO and H40) were encapsulated in the core while the hydrophilic components (mPEG-CHO) were acted as the shell. The final AIE-active H40-mPEG-mPTH LPNs displayed uniform spherical structure, strong fluorescence, excellent photostability and high water dispersity. Furthermore, biological evaluation results demonstrated that H40-mPEG-mPTH LPNs possess low toxicity and excellent biocompatibility, indicating their great potential for biomedical applications. Taken together, we reported a novel strategy for the construction of hyperbranched and biodegradable LPNs with AIE feature through a one-step acetalization reaction, which can be also utilized for construction of many other AIE-active LPNs with a variety structure and properties.

Facile synthesis of polymeric fluorescent organic nanoparticles based on the self-polymerization of dopamine for biological imaging.

Polymeric fluorescent organic nanoparticles (polymer-FONs) have raised considerable research attention for biomedical applications owing to their advantages as compared with fluorescent inorganic nanoparticles and small organic molecules. In this study, we presented an efficient, facile and environment-friendly strategy to produce polymer-FONs, which relied on the self-polymerization of dopamine and polyethyleneimine (PEI) in rather mild conditions. To obtain the final polymer-FONs, aldehyde group-containing copolymers (named as poly(UA-co-PEGMA)) were synthesized by reversible addition-fragmentation chain-transfer polymerization using polyethylene glycol methyl ether methacrylate (PEGMA) and 1-undecen-10-al (UA) as monomers. The dopamine was conjugated onto poly(UA-co-PEGMA) through a multicomponent reaction between UA and dopamine to obtain poly(UA-co-PEGMA)-DA, which was further utilized for preparation of polymer-FONs through self-polymerization of dopamine and PEI. 1H nuclear magnetic resonance, Fourier transform infrared spectroscopy, transmission electron microscopy and fluorescence spectroscopy were employed to characterize the structure, morphology, compositions and optical properties of these polymer-FONs. Cell viability and cell uptake behavior results suggested that these polymer-FONs possess good biocompatibility and can be potentially utilized for biomedical applications. More importantly, the method can be also applied to fabricate many other multifunctional polymer-FONs with great potential for biomedical applications.

Polymerizable aggregation-induced emission dye for preparation of cross-linkable fluorescent nanoprobes with ultra-low critical micelle concentrations.

In recent years, aggregation-induced emission (AIE) dyes based fluorescent organic nanoparticles (FONs) have achieved significant progress in various biomedical applications. In this work, we developed a covalent strategy to prepare biocompatible AIE-active dyes based cross-linked copolymers (MPC-POSS-PhE) via controllable reversible addition fragmentation chain transfer (RAFT) polymerization using zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC), polymerizable AIE dye (named as PhE) and 8-vinyl polyoctahedral silsesquioxanes (POSS) as monomers. Due to the existence of hydrophilic MPC and hydrophobic PhE, the resultant copolymers will self-assemble into core-shell nanoparticles in aqueous solution with ultra-low critical micelle concentration (CMC). This could effectively overcome the drawbacks of non-crosslinked micelles and show more attractive properties and better performance for biomedical applications. Furthermore, the characterization results and biological assays demonstrated that the final MPC-POSS-PhE FONs show stable aqueous stability, uniform size and morphology, high water dispersity, desirable optical properties and low cytotoxicity. These remarkable properties make the resultant AIE-active nanoprobes great potential for biomedical applications.

Facile Fabrication of AIE-Active Fluorescent Polymeric Nanoparticles with Ultra-Low Critical Micelle Concentration Based on Ce(IV) Redox Polymerization for Biological Imaging Applications.

Fluorescent polymeric nanoparticles (FPNs) with aggregation-induced emission (AIE) property have received increasing attention and possess promising biomedical application potential in the recent years. Many efforts have been devoted to the fabrication methodologies of FPNs and significant advance has been achieved. In this contribution, a novel strategy for the fabrication of AIE-active amphiphilic copolymers is reported for the first time based on the Ce(IV) redox polymerization. As an example, ene group containing AIE-active dye (named as Phe-alc) is directly grafted onto a water soluble polymer polyethylene glycol (PEG) in H2 O/THF system under low temperature. Thus-obtained amphiphilic fluorescent polymers will self-assemble into FPNs with ultra-low critical micelle concentration, ultra-brightness, and great water dispersibility. Biological evaluation results suggest that the PEG-poly(Phe-alc) possess excellent biocompatibility and can be used for tracing their behavior in cells using confocal laser scanning microscope. These features make PEG-poly(Phe-alc) FPNs promising candidates for many biomedical applications, such as cell imaging, drug delivery vehicles, and targeted tracing. More importantly, many other functional groups can also be incorporated into these AIE-active FPNs through the redox polymerization. Therefore, the redox polymerization should be a facile and effective strategy for fabrication of AIE-active FPNs.

Recent progress and development on polymeric nanomaterials for photothermal therapy: a brief overview.

Photothermal therapy (PTT) is a rapidly expanding area which has attracted great research attention, and has emerged as a promising method for cancer treatment recently. PTT mainly relies on the local heating effect from photothermal agents (PTAs), which can transform the energy of light into heat. Various inorganic PTAs such as gold nanorods, carbon nanomaterials, layered transition metal dichalcogenides and various polymeric nanomaterials have been developed for PTT applications. However, inorganic PTAs are normally poorly biodegradable and potentially toxic. Polymeric PTAs possess many advantages in comparison with inorganic PTAs and have become the focus for PTT applications very recently. In this article, the recent advances and progress of polymers such as conjugated polymers and melanin-like polymers for PTT applications are introduced. The future direction, challenges and potential development of polymeric PTAs for efficient PTT are also addressed. The objective of this review is to give a brief overview of this emerging field to polymer chemists and material scientists.