As a mussel-inspired material, polydopamine (PDA), possesses many properties, such as a simple preparation process, good biocompatibility, strong adhesive property, easy functionalization, outstanding photothermal conversion efficiency, and strong quenching effect. PDA has attracted increasingly considerable attention because it provides a simple and versatile approach to functionalize material surfaces for obtaining a variety of multifunctional nanomaterials. In this review, recent significant research developments of PDA including its synthesis and polymerization mechanism, physicochemical properties, different nano/microstructures, and diverse applications are summarized and discussed. For the sections of its applications in surface modification and biomedicine, we mainly highlight the achievements in the past few years (2016-2019). The remaining challenges and future perspectives of PDA-based nanoplatforms are discussed rationally at the end. This timely and overall review should be desirable for a wide range of scientists and facilitate further development of surface coating methods and the production of PDA-based materials.

Versatile Polydopamine Platforms: Synthesis and Promising Applications for Surface Modification and Advanced Nanomedicine

Recent progress in drug delivery

In this study, we introduced a targeting polymer poly(ethylene glycol)–folic acid (PEG–FA) on the surface of polydopamine (PDA)-modified mesoporous silica nanoparticles (MSNs) to develop the novel nanoparticles (NPs) MSNs@PDA–PEG–FA, which were employed as a drug delivery system loaded with doxorubicin (DOX) as a model drug for cervical cancer therapy. The chemical structure and properties of these NPs were characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, N2 adsorption/desorption, dynamic light scattering-autosizer, thermogravimetric analysis, and Fourier transform infrared spectroscopy. The pH-sensitive PDA coating served as a gatekeeper. The in vitro drug release experiments showed pH-dependent and sustained drug release profiles that could enhance the therapeutic anticancer effect and minimize potential damage to normal cells due to the acidic microenvironment of the tumor. These MSNs@PDA–PEG–FA achieved significantly high targeting efficiency, which was demonstrated...

pH-Sensitive Delivery Vehicle Based on Folic Acid-Conjugated Polydopamine-Modified Mesoporous Silica Nanoparticles for Targeted Cancer Therapy

D-ɑ-tocopheryl polyethylene glycol succinate (Vitamin E TPGS or TPGS) has been approved by FDA as a safe adjuvant and widely used in drug delivery systems. The biological and physicochemical properties of TPGS provide multiple advantages for its applications in drug delivery like high biocompatibility, enhancement of drug solubility, improvement of drug permeation and selective antitumor activity. Notably, TPGS can inhibit the activity of ATP dependent P-glycoprotein and act as a potent excipient for overcoming multi-drug resistance (MDR) in tumor. In this review, we aim to discuss the recent advances of TPGS in drug delivery including TPGS based prodrugs, nitric oxide donor and polymers, and unmodified TPGS based formulations. These potential applications are focused on enhancing delivery efficiency as well as the therapeutic effect of agents, especially on overcoming MDR of tumors. It also demonstrates that the clinical translation of TPGS based nanomedicines is still faced with many challenges, which requires more detailed study on TPGS properties and based delivery system in the future.

Recent Advances in the Application of Vitamin E TPGS for Drug Delivery.

Synergistic therapy that combines chemo-, gene-, or photothermal means shows great potential for enhancing the therapeutic effects on cancers. Tumor-targeted nanoparticles based on a doxorubicin (DOX)-gated mesoporous silica nanocore (MSN) encapsulated with permeability glycoprotein (P-gp) small interfering RNA (siRNA) and a polydopamine (PDA) outer layer for DOX loading and folic acid decoration are designed. The multifunctional nanoplatform tactfully integrates chemo- (DOX), gene- (P-gp siRNA), and photothermal (PDA layer) substances in one system. In vitro results reveal that DOX release behaviors are both pH- and thermal-responsive and the release of co-delivered P-gp siRNA is also pH-dependent due to the pH-cleavable DOX gatekeeper on MSN. In addition, due to the near-infrared light-responsive PDA outer layer and folic acid conjugation, the nanoparticles exhibit outstanding photothermal activity and selective cell targeting ability. Subsequently, in vitro and in vivo antitumor experiments both demonstrate the enhanced antitumor efficacy of the multifunctional nanoparticles, indicating the significance of synergistic therapy combining chemo-, gene-, and photothermal treatments in one system.

A Multifunctional Nanoplatform against Multidrug Resistant Cancer: Merging the Best of Targeted Chemo/Gene/Photothermal Therapy

A nanocarrier system of d-a-tocopheryl polyethylene glycol 1000 succinate (TPGS)-functionalized polydopamine-coated mesoporous silica nanoparticles (NPs) is developed for sustainable and pH-responsive delivery of doxorubicin (DOX) as a model drug for the treatment of drug-resistant nonsmall cell lung cancer. Such nanoparticles are of desired particle size, drug loading, and drug release profile. The surface morphology, surface charge, and surface chemical properties are also successfully characterized by a series of techniques such as transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), Brunauer-Emmett-Teller (BET) method, thermal gravimetric analysis (TGA), dynamic light scattering (DLS), and Fourier transform infrared spectroscopy (FTIR). The normal A549 cells and drug-resistant A549 cells are employed to access the cytotoxicity and cellular uptake of the NPs. The therapeutic effects of TPGS-conjugated nanoparticles are evaluated in vitro and in vivo. Compared with free DOX and DOX-loaded NPs without TPGS ligand modification, MSNs-DOX@PDA-TPGS exhibits outstanding capacity to overcome multidrug resistance and shows better in vivo therapeutic efficacy. This splendid drug delivery platform can also be sued to deliver other hydrophilic and hydrophobic drugs.

TPGS-Functionalized Polydopamine-Modified Mesoporous Silica as Drug Nanocarriers for Enhanced Lung Cancer Chemotherapy against Multidrug Resistance.

The efficient delivery of anticancer drugs into tumor tissues to improve therapeutic efficacy remains an urgent demand. To satisfy this demand, a drug delivery system based on a stealthy nanocapsule was developed. This nanocapsule was fabricated by encapsulating stealthy cross-linked poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) and benzaldehyde groups around the protein bovine serum albumin (BSA) followed by conjugation of doxorubicin (Dox) through a pH-responsive benzoic-imine bond. The in vitro results show that the Dox-conjugated nanocapsule (nBSA-Dox) released the drug under an acidic tumor microenvironment (pH ~6.5) and killed HepG2 human liver cancer cells. The half-life of Dox conjugated to nBSA in mice was significantly prolonged, and the area-under-curve of plasma Dox of the mice treated with nBSA-Dox was as much as 242 fold of free Dox. The in vivo results confirmed that this nanocapsule efficiently accumulated in tumor tissue and significantly suppressed the tumor growth.

/pdf/phosphorylcholine-based-stealthy-nanocapsules-enabling-tumor-4kh9oss9ko.pdf

Phosphorylcholine-based stealthy nanocapsules enabling tumor microenvironment-responsive doxorubicin release for tumor suppression

Combining sufficient stability during circulation and desirable drug release is still a great challenge for the clinical applications of nanocarriers. To satisfy this demand, we developed a novel unimolecular micelle (UM) to deliver the antitumor agent 1,2-diaminocyclohexane-platinum(II) (DACHPt) for enhanced therapy of lung cancer. This DACHPt-loaded UM (UM/DACHPt) was formed through chelate complexation between DACHPt and a hydrophilic and biodegradable dendritic block copolymer poly(amidoamine)-polyglutamic acid-b-polyethylene glycol (PAM-PGlu-b-PEG), which was composed of generation 3 PAMAM (PAMAM-G3), polyglutamic acid, and long-circulating polymer PEG. This UM/DACHPt displayed robust stability and would effectively inhibit the undesired release under physiological condition, thus exhibiting much longer in vivo half-life than diblock copolymer micelles. With significant in vitro cell cytotoxicity to A549 lung cancer cells, this UM/DACHPt demonstrated efficient antitumor efficacy on an A549 xenograft ...

DACHPt-Loaded Unimolecular Micelles Based on Hydrophilic Dendritic Block Copolymers for Enhanced Therapy of Lung Cancer

Cancer Therapy: TPGS-Functionalized Polydopamine-Modified Mesoporous Silica as Drug Nanocarriers for Enhanced Lung Cancer Chemotherapy against Multidrug Resistance (Small 29/2017)

The invention provides a dendritic block copolymer PAM-PGlu-b-TPGS and its preparation method and use. The dendritic block copolymer PAM-PGlu-b-TPGS has a structure shown in the formula I. In the formula I, n, PAM, TPGS and p are defined in the specification. The dendritic block copolymer PAM-PGlu-b-TPGS can be effectively used as a pharmaceutic adjuvant for drug preparation and be especially used as a drug-loading nanoparticle and a drug-loading microsphere.

Yixiong Zuo

Papers

TPGS-Functionalized Polydopamine-Modified Mesoporous Silica as Drug Nanocarriers for Enhanced Lung Cancer Chemotherapy against Multidrug Resistance.

Phosphorylcholine-based stealthy nanocapsules enabling tumor microenvironment-responsive doxorubicin release for tumor suppression

DACHPt-Loaded Unimolecular Micelles Based on Hydrophilic Dendritic Block Copolymers for Enhanced Therapy of Lung Cancer

Cancer Therapy: TPGS-Functionalized Polydopamine-Modified Mesoporous Silica as Drug Nanocarriers for Enhanced Lung Cancer Chemotherapy against Multidrug Resistance (Small 29/2017)

Dendritic block copolymer PAM-PGlu-b-TPGS and its preparation method and use