Zibiao Li

Recent Advances of Using Hybrid Nanocarriers in Remotely Controlled Therapeutic Delivery

The development of hybrid biomaterials has been attracting great attention in the design of materials for biomedicine. The nanosized level of inorganic and organic or even bioactive components can be combined into a single material by this approach, which has created entirely new advanced compositions with truly unique properties for drug delivery. The recent advances in using hybrid nanovehicles as remotely controlled therapeutic delivery carriers are summarized with respect to different nanostructures, including hybrid host-guest nanoconjugates, micelles, nanogels, core-shell nanoparticles, liposomes, mesoporous silica, and hollow nanoconstructions. In addition, the controlled release of guest molecules from these hybrid nanovehicles in response to various remote stimuli such as alternating magnetic field, near infrared, or ultrasound triggers is further summarized to introduce the different mechanisms of remotely triggered release behavior. Through proper chemical functionalization, the hybrid nanovehicle system can be further endowed with many new properties toward specific biomedical applications.

Recent progress of atomic layer deposition on polymeric materials

As a very promising surface coating technology, atomic layer deposition (ALD) can be used to modify the surfaces of polymeric materials for improving their functions and expanding their application areas. Polymeric materials vary in surface functional groups (number and type), surface morphology and internal structure, and thus ALD deposition conditions that typically work on a normal solid surface, usually do not work on a polymeric material surface. To date, a large variety of research has been carried out to investigate ALD deposition on various polymeric materials. This paper aims to provide an in-depth review of ALD deposition on polymeric materials and its applications. Through this review, we will provide a better understanding of surface chemistry and reaction mechanism for controlled surface modification of polymeric materials by ALD. The integrated knowledge can aid in devising an improved way in the reaction between reactant precursors and polymer functional groups/polymer backbones, which will in turn open new opportunities in processing ALD materials for better inorganic/organic film integration and potential applications.

Long-Term Real-Time In Vivo Drug Release Monitoring with AIE Thermogelling Polymer

A new drug concentration meter is developed. In vivo drug release can be monitored precisely via a self-indicating drug delivery system consisting of a new aggregation-induced emission thermoresponsive hydrogel. By taking the advantage of a self-indicating system, one can easily detect the depletion of drugs, and reinject to maintain a dosage in the optimal therapeutic window.

Towards the development of polycaprolactone based amphiphilic block copolymers: molecular design, self-assembly and biomedical applications

Polycaprolactone (PCL) and its copolymers are a type of hydrophobic aliphatic polyester based on hydroxyalkanoic acids. They possess exceptional qualities: biocompatibility; FDA approval for clinical use; biodegradability by enzyme and hydrolysis under physiological conditions and low immunogenicity. These critical properties have facilitated their value as sutures, drug delivery vehicles and tissue engineering scaffolds in pharmaceutical and biomedical applications. However, the hydrophobicity of PCL and its copolymers remains a concern for further biological and biomedical applications. One promising approach is to design and synthesize well-controlled PCL-based amphiphilic block copolymers. This review summarizes recent advances in the synthesis and self-assembly of PCL-containing amphiphilic block copolymers and their bio-related applications including drug delivery and tissue engineering.

Safe and efficient membrane permeabilizing polymers based on PLLA for antibacterial applications

Poly(N,N-dimethylaminoethyl methacrylate)-block-poly(L-lactic acid)-block-poly(N,N-dimethylaminoethyl methacrylate) conjugated with poly(ethylene glycol) (D-PLLA-D@PEG) copolymers were synthesized. These non-aggregating polymers showed low MIC values against Gram-negative and Gram-positive, including methicillin-resistant Staphylococcus aureus (MRSA), bacteria. The polymers exhibited minimal toxicity and are promising antibacterial agents for biomedical applications.

Emerging Supramolecular Therapeutic Carriers Based on Host–Guest Interactions

Recent advances in host-guest chemistry have significantly influenced the construction of supramolecular soft biomaterials. The highly selective and non-covalent interactions provide vast possibilities of manipulating supramolecular self-assemblies at the molecular level, allowing a rational design to control the sizes and morphologies of the resultant objects as carrier vehicles in a delivery system. In this Focus Review, the most recent developments of supramolecular self-assemblies through host-guest inclusion, including nanoparticles, micelles, vesicles, hydrogels, and various stimuli-responsive morphology transition materials are presented. These sophisticated materials with diverse functions, oriented towards therapeutic agent delivery, are further summarized into several active domains in the areas of drug delivery, gene delivery, co-delivery and site-specific targeting deliveries. Finally, the possible strategies for future design of multifunctional delivery carriers by combining host-guest chemistry with biological interface science are proposed.

Recent development of unimolecular micelles as functional materials and applications

Unimolecular micelles have attracted increasing attention due to their high functionality, encapsulation and site specific confinement capabilities in various applications. Compared to conventional supramolecular micelles, unimolecular micelles possess unique single molecular architectures which can maintain excellent stability when they are subjected to extreme surrounding environment changes such as high dilution and alterations in temperature, pH, ionic strength etc. In this review, the most recent advances in the design strategies of unimolecular micelles are presented with respect to different types of architectural polymers, including dendrimers, and hyperbranched, dendritic, star, brush-like and amphiphilic cyclic polymers. The diverse functions of these sophisticated materials endow a biosignificance in therapeutic agent delivery. And the use of unimolecular micelles as templates for inorganic nanoparticle preparation, catalysis, and energy harvesting are also summarized in this review. Finally, the challenges for the facile fabrication of unimolecular micelles and future perspectives are also discussed.

PHB-Based Gels as Delivery Agents of Chemotherapeutics for the Effective Shrinkage of Tumors

Injectable thermogel to deliver chemotherapeutics in a minimally invasive manner and to achieve their long term sustained release at tumor sites to minimize side effects is attractive for chemotherapy and precision medicine, but its rational design remains a challenge. In this work, a copolymer with natural biodegradable poly[(R)-3-hydroxybutyrate] (PHB), hydrophilic poly(ethylene glycol), and temperature sensitive poly(propylene glycol) blocks linked by urethane linkages is designed to show thermogelling characteristics which are beneficial for minimally invasive injection and safe degradation. This thermogelling polymer possesses in vitro biocompatibility with very low cyto-toxicity in HEK293 cells. Furthermore, it is able to form the gel to achieve the controllable release of paclitaxel (PTX) and doxorubicin (DOX) by adjusting polymer concentrations. A rodent model of hepatocarcinoma has been performed to demonstrate the in vivo applications of this PHB-based thermogel. The drug-loaded thermogel has been intratumorally injected and both PTX-loaded and DOX-loaded thermogel have significantly slowed down tumor growth. This work represents the first time that injectable PHB thermogels have possessed good controllable release effect of chemotherapeutics against the in vivo model of tumors and will benefit various applications, including on-demand drug delivery and personalized medicine.

Poly(ethylene glycol) Conjugated Poly(lactide)-Based Polyelectrolytes: Synthesis and Formation of Stable Self-Assemblies Induced by Stereocomplexation

A series of pH-responsive amphiphilic poly(N,N-dimethylaminoethyl methacrylate)-block-poly(D-lactic acid)-block-poly(N,N-dimethylaminoethyl methacrylate) conjugated with poly(ethylene glycol) (D-PDLA-D@PEG) and D-PLLA-D@PEG copolymers were synthesized using a combination of ring-opening polymerization and atom-transfer radical polymerization followed by sequential quaternization of PDMAEMA chains and azide-alkyne click reaction with alkyne-end PEG. Gel permeation chromatography, nuclear magnetic resonance, and Fourier transform infrared spectroscopy results demonstrate the successful synthesis of the copolymers, and the conjugated PEG percentages in the copolymers can be tuned by the feeding ratios in the quaternization reaction. Conjugating PEG onto the PDMAEMA segments also successfully facilitated the D-PDLA-D@PEG, D-PLLA-D@PEG, and its corresponding 1:1 D/L mixtures to be dissolved directly in aqueous solution at the desired concentration range without using any organic solvents unlike the copolymers without PEG conjugation (D-PDLA-D and D-PLLA-D). We demonstrate control over micellar size, charge, and stability via three different preparation pathways, i.e., solution pH, percentages of PEG conjugation in the copolymers, and formation of PLA stereocomplex in micellar core. Static and dynamic light scattering studies demonstrate that the size of the core-shell micelles increases when the solution pH is reduced due to the protonation of the PDMAEMA segments that caused the osmotic pressure within the micelle to increase until the micelles reached a maximum size. It is interesting to note that the micelles formed by 1:1 D/L mixtures have larger swelling ratios as well as aggregation number and hydrodynamic radius that do not change significantly with pH and dilution, respectively, as compared to micelles formed from individual D or L forms of the copolymers. The enhanced stability of the pH-responsive micelles prepared by direct dissolution of the 1:1 D/L mixtures of the PEG conjugated PLA-based polyelectrolytes in aqueous medium is attributed to the stereocomplex formation between PLLA and PDLA in the micellar core as confirmed by wide-angle X-ray scattering measurements.

Facile Layer-by-Layer Self-Assembly toward Enantiomeric Poly(lactide) Stereocomplex Coated Magnetite Nanocarrier for Highly Tunable Drug Deliveries

A highly tunable nanoparticle (NP) system with multifunctionalities was developed as drug nanocarrier via a facile layer-by-layer (LbL) stereocomplex (SC) self-assembly of enantiomeric poly(l-lactic acid) (PLLA) and poly(d-lactic acid) (PDLA) in solution using silica-coated magnetite (Fe3O4@SiO2) as template. The poly(lactide) (PLA) SC coated NPs (Fe3O4@SiO2@-SC) were further endowed with different stimuli-responsiveness by controlling the outermost layer coatings with respective pH-sensitive poly(lactic acid)-poly(2-dimethylaminoethyl methacrylate) (PLA-D) and temperature-sensitive poly(lactic acid)-poly(N-isopropylacrylamide) (PLA-N) diblock copolymers to yield Fe3O4@SiO2@SC-D and Fe3O4@SiO2@SC-N NPs, respectively, while the superparamagnetic properties of Fe3O4 were maintained. TEM images show a clearly resolved core-shell structure with a silica layer and sequential PLA SC co/polymer coating layers in the respective NPs. The well-designed NPs possess a size distribution in a range of 220-270 nm and high magnetization of 70.8-72.1 emu/g [Fe3O4]. More importantly, a drug release study from the as-constructed stimuli-responsive NPs exhibited sustained release profiles and the rates of release can be tuned by variation of external environments. Further cytotoxicity and cell culture studies revealed that PLA SC coated NPs possessed good cell biocompatibility and the doxorubicin (DOX)-loaded NPs showed enhanced drug delivery efficiency toward MCF-7 cancer cells. Together with the strong magnetic sensitivity, the developed hybrid NPs demonstrate a great potential of control over the drug release at a targeted site. The developed coating method can be further optimized to finely tune the nanocarrier size and operating range of pHs and temperatures for in vivo applications.