Wenhai Lin

The use of cisplatin-loaded mucoadhesive nanofibers for local chemotherapy of cervical cancers in mice

Polymer-based local drug delivery system may be suitable for the treatment of cervix cancer. A pilot study was carried out to examine the efficacy of cisplatin-loaded poly(ethylene oxide)/polylactide composite electrospun nanofibers as a local chemotherapy system against cervical cancer in mice via vaginal implantation. The nanofibers were proven to have good mucoadhesive property by in vitro mucoadhesion test and in vivo vaginal retention evaluation. An orthotopic cervical/vaginal cancer model was established by injecting murine cervical cancer U14 cells into the vaginal submucosa nearby the cervix. By inserting the nanofibers mat into the vagina of mice, the cisplatin released from the fiber-mat showed a much more accumulation in the vagina/cervix region than in the peripheral organs such as kidneys, liver, or blood, in contrary to the case of intravenous (i.v) injection. The in vivo trials showed that a better balance between anti-tumor efficacy and systemic safety was achieved in nanofibers group than that in i.v injection group at the equal drug dose. Therefore, electrospun nanofibers present a promising approach to the local drug delivery via vagina against cervical cancer.

Near-Infrared Emitting Fluorescent BODIPY Nanovesicles for in Vivo Molecular Imaging and Drug Delivery

Near-infrared fluorescent nanovesicles were prepared by self-assembly of block copolymer hydrophilic poly(ethylene glycol) boron-dipyrromethenes in aqueous solution. The fluorescence enhancement induced by dissociation of nanovesicles could be used as a smart imaging and diagnostic tool. This nanovesicle could encapsulate the antitumor drug, and provide a powerful platform for imaging-guided tumor-specific drug delivery and therapy.

Reduction-sensitive amphiphilic copolymers made via multi-component Passerini reaction for drug delivery.

One-step synthesis of amphiphilic polymers containing disulfide bond within the hydrophobic backbone was demonstrated via multi-component Passerini reaction. The obtained polymer was self-assembled into micelles in aqueous solution. Curcumin (CUR), an effective and safe anticancer agent, which was limited by its water insolubility and poor bioavailability, was loaded into the micelles as a model drug. The nanoscale polymeric micelles were confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Faster intracellular CUR release was observed by confocal laser scanning microscopy (CLSM) in the HeLa cells pretreated with GSH than in the unpretreated ones. Micelles also loaded with NH2-BODIPY which was almost non-fluorescent and gave strong enhanced fluorescence under acid conditions. The phenomenon of the stronger enhanced fluorescence in the pretreated HeLa cells showed further that the obtained polymer was reduction-sensitive. In vitro MTT assays showed that the micelles were biocompatible and CUR-loaded micelles had higher cellular proliferation inhibition in contrast to free CUR toward HeLa cells. These results highlight the potential of using multi-component Passerini reaction to make functional copolymers as smart nanocarriers for drug delivery.

Near-Infrared Polymeric Nanoparticles with High Content of Cyanine for Bimodal Imaging and Photothermal Therapy

The discovery and synthesis of theranostic nanomedicines with high loading of imaging and therapeutic agents is challenging. In this work, a polymer assembling strategy was used to make nanoparticles with exceptionally high loading of theranostic agent. As an example, poly(heptamethine) was synthesized via multicomponent Passerini reaction, and then assembled into nanoparticles in the presence of poly(ethylene glycol)2k-block-poly(d,l-lactide)2k (PEG-PLA) with high heptamethine loading (>50%). The formed nanoparticles could be used for bimodal bioimaging and photothermal therapy. The bimodal bioimaging provided complementary message about biodistribution, and photothermal treatment inhibited the growth of cervical carcinoma upon laser irradiation. This assembly of polymers formed by imaging and therapeutic agents opens new possibilities for the construction of multifunctional nanomedicines.

Paclitaxel prodrug nanoparticles combining chemical conjugation and physical entrapment for enhanced antitumor efficacy

This study presents the combination of the prodrug approach with the self-assembly technique by using a poly(ethylene glycol)–paclitaxel (PTX) conjugate as the nanomicellar carrier for delivery of free PTX drugs. The conjugate PEG-PCPGE/PTX readily forms stable micelles in aqueous solution and is used to form an intracellular pool of PTX after the micelles are endocytosed, where encapsulated drug is first released, then destabilized polymer–PTX molecules liberate free PTX following cleavage in the intracellular environment. The use of the conjugate PTX as the core of the micelles provides an ideal affinity site for free PTX, in the mean time, high drug loading and time-programmable delivery are realized.

Effect of Molecular Structure on Stability of Organic Nanoparticles Formed by Bodipy Dimers

The objective was to evaluate the stability of organic nanoparticles made from Bodipy dimers. Bodipy dimers with different length of linkers were synthesized via multicomponent Passerini reaction, and could form the fluorescent nanoparticles (FNPs) through nanoprecipitation. Bodipy-dimers FNPs with long chain linker indicated better stability in biological condition than those with short one as revealed by changes of diameter and size distribution. The FNPs possessed high physical homogeneity and low cytotoxicity. The molecular structure dependent stability was also validated by confocal laser scanning microscope based on the dissociation-induced fluorescence recovering. Importantly, stable FNPs also could be used to load hydrophobic cargoes and deliver them into cytoplasm. We believe this systematic study between structure and stability might open new opportunities for designing stable nanoparticles for various applications.

Synthesis of cross-linked polymers via multi-component Passerini reaction and their application as efficient photocatalysts

One-step synthesis of cross-linked polymers containing Ru complexes (Ru-CPs) is demonstrated via multi-component Passerini reaction. Ru-CPs were shown to be highly effective and recyclable heterogeneous photocatalysts for oxidation of thioanisole and benzyl amine.

Amphiphilic Drug‐Dye Conjugates Assembled Nanoparticles for Imaging and Chemotherapy

An amphiphilic drug-dye conjugate (PTX-Pt-BDP) was designed and synthesized with a platinum compound as the hydrophilic head. The precursor of PTX-Pt-BDP was obtained under mild conditions by means of a three-component Passerini reaction. PTX-Pt-BDP could self-assemble into nanoparticles (PTX-Pt-BDP NPs) in aqueous solution via a nanoprecipitation method. The obtained nanoparticles exhibited favorable structural stability in both water and physiological environment. PTX-Pt-BDP NPs could be endocytosed by cancer cells as revealed by confocal laser scanning microscopy and exert potent cytotoxicity. This work highlights the potential of nanomedicines from amphiphilic drug-dye conjugates for cancer cell imaging and chemotherapy.

Rational Design of Polymeric Nanoparticles with Tailorable Biomedical Functions for Cancer Therapy

Polymeric nanoparticles (NPs) play a key role in nanoscale formulations for bioimaging, cancer treatment, and theranostics. In this work, we designed and synthesized a series of hydrophobic polymers (P1-6) with different pendent groups via one-step multicomponent Passerini reaction. These polymers possessed similar molecular structures and various biomedical functions. Interestingly, they could self-assemble into stable NPs in aqueous media. All formed NPs were redox sensitive because of the existence of disulfide bonds in the backbone. The stability of NPs in aqueous media with or without glutathione was systematically evaluated and compared. The optical performance, including fluorescence resonance energy transfer, was characterized under different conditions for those polymers with fluorescent components. Importantly, all formed NPs showed good cytocompatibility toward HeLa cells and different biological functions, including drug loading and delivery, bioimaging with variable fluorescence, and photodynamic activity, as evidenced by experiments in vitro and in vivo. These results demonstrate the great potential of multicomponent reaction to customize versatile polymeric nanoparticles for biomedical applications.

Amphiphilic redox-sensitive NIR BODIPY nanoparticles for dual-mode imaging and photothermal therapy

Theranostics, integrating tumor treatment and diagnosis concurrently, has become an emerging and meaningful strategy in cancer therapy. In this work, an amphiphilic redox-sensitive near-infrared (NIR) BODIPY dye, which could be formed into nanoparticles (PEG-SS-BDP NPs) by self-assembly, was synthesized and possessed good capability of photothermal therapy (PTT), near-infrared fluorescence (NIRF) imaging, photoacoustic (PA) imaging and drug loading. The stable nanoparticles could be dissociated to turn on NIRF due to the rift of embedded disulfide bonds by glutathione (GSH). The enhanced fluorescence in vitro could be observed via confocal laser scanning microscopy (CLSM) after adding GSH, confirming the redox-sensitivity of disulfide bonds. NIRF and PA imaging demonstrated active accumulation in tumor and good imaging effect. At last, PEG-SS-BDP NPs could significantly suppress tumor growth in vivo upon irradiation. The amphiphilic redox-sensitive BODIPY nanoparticles provide a promising design strategy to formulate multifunctional stimuli-responsive theranostic nanoplatforms.