Application of cell membrane-functionalized biomimetic nanoparticles in the treatment of glioma.

Glioma is one of the most common malignant tumors with characteristics of strong invasion and high postoperative recurrence rate, which seriously threatens human health. Nanoparticles as an emerging drug delivery system have promoted the development of glioma therapy. However, blocking of nanoparticles by the blood-brain barrier is still serious problem for the use of nanoparticles in glioma therapy. In this context, traditional nanoparticles are dressed with natural cell membranes to prepare biomimetic nanoparticles. Biomimetic nanoparticles show longer blood circulation time, excellent homologous targeting and outstanding immune escape capacity, which significantly improve the accumulation of nanoparticles at the tumor site. The therapeutic effect for glioma has been raised to an advanced level. This review focuses on the preparations and applications of cell membrane-functionalized biomimetic nanoparticles, as while as the advantages and problems of biomimetic nanoparticles in the treatment of glioma. In particular, the approach of using biomimetic nanoparticles to cross the blood-brain barrier is analyzed, in the hope of providing new ideas for further developments in crossing the blood-brain barrier and in glioma therapy.

Co-delivery of paclitaxel and doxorubicin using polypeptide-engineered nanogels for combination therapy of tumor.

Loading of chemotherapeutic agents into nanoparticles has been demonstrated to be an effective strategy for cancer therapy. However, simultaneous delivery of different functional drugs to tumor sites for chemotherapy still remains challenging. In this study, nanogels formed by an engineered coiled-coil polypeptide PC10A were designed and prepared as a carrier for co-delivery of paclitaxel (PTX) and doxorubicin (DOX) through ultrasonic treatment and electrostatic adsorption. The drug loading content and encapsulation efficiency of PTX and DOX in the PC10A/PTX/DOX nanogels were 5.98 wt%, 70 wt%, and 8.55 wt%, 83 wt%, respectively. Because the polypeptide PC10A was non-toxic and biodegradable, the PC10A/PTX/DOX nanogels exhibited good biocompatibility. Thein vitroandin vivoantitumor experiments showed that the PC10A/PTX/DOX nanogels possessed obviously synergistic therapy effect of tumors and lower side effects compared with free PTX/DOX. Therefore, the PC10A/PTX/DOX nanogels are promising to provide a new strategy for combination therapy of different functional drugs.

Antitumor immunity triggered by photothermal therapy and photodynamic therapy of a 2D MoS2 nanosheet-incorporated injectable polypeptide-engineered hydrogel combinated with chemotherapy for 4T1 breast tumor therapy.

A multifunctional PC10A/DOX/MoS2 hydrogel was designed and prepared for chemotherapy/photothermal therapy/photodynamic therapy of 4T1 tumor, and the immune responses triggered by photothermal and photodynamic effect of MoS2 nanosheet in the hydrogel were also studied. Positively charged DOX and negatively charged PC10A were loaded on the surface of MoS2 nanosheet through layer-by-layer method to prepare hybrid PC10A/DOX/MoS2 nanoparticles. PC10A/DOX/MoS2 nanoparticles were dispersed in PC10A hydrogel to prepare PC10A/DOX/MoS2 hydrogel. 2D MoS2 nanosheet in the hydrogel was simultaneously utilized as photothermal agent and photodynamic agent for the generation of hyperthermia and reactive oxygen species, respectively. This PC10A/DOX/MoS2 hydrogel was injectable and possessed excellent biocompatibility. The results of in vivo tumor-bearing mice experiments showed that a remarkably enhance tumor inhibition was observed by the combination of chemo-photothermal-photodynamic therapy compared with photothermal therapy, photodynamic therapy, or chemotherapy alone. In addition, the results of in vivo therapy exhibited that the PC10A/DOX/MoS2 hydrogel with laser irradiation could activate antitumor immune effects to suppress the growth of primary 4T1 breast tumors and distal lung metastatic nodules. Therefore, these results demonstrated that the PC10A/DOX/MoS2 hydrogel was promising to be utilized in antitumor immunity therapy triggered by photothermal therapy and photodynamic therapy for malignant tumor.

Hollow gold nanoshells-incorporated injectable genetically engineered hydrogel for sustained chemo-photothermal therapy of tumor.

BACKGROUND: Combined therapy has demonstrated to be an effective strategy for cancer therapy. Herein, an injectable hydrogel based on the genetically engineered polypeptide and hollow gold nanoshells (HAuNS) has been developed for chemo-photothermal therapy of HepG2 tumor. METHODS: PC10A/DOX/HAuNS nanogel was prepared with layer-by-layer through the adsorption of DOX and PC10A successively. DOX with positive charge and PC10A with negative charge were coated step by step onto the surface of negatively charged HAuNS. The multifunctional hydrogel PC10A/DOX/HAuNS were prepared via dissolving hybrid PC10A/DOX/HAuNS nanogel in polypeptide PC10A. Chemotherapy drug DOX in the PC10A/DOX/HAuNS hydrogel was absorbed on the HAuNS and directly embedded in the PC10A hydrogel, which contributes to sequentially release of the drug. Specifically, DOX adsorbed on the HAuNS could be released slowly for sustainable chemotherapy. RESULTS: The PC10A/DOX/HAuNS hydrogel could pass 26-gauge needle without clogging, indicating that it is injectable. In addition, the PC10A/DOX/HAuNS hydrogel possessed outstanding photothermal effect and photothermal stability. In both in vitro cell and in vivo tumor-bearing mice experiments, a remarkably enhance tumor inhibition was observed by the combined therapy of chemo-photothermal therapy compared with photothermal therapy or chemotherapy alone. CONCLUSIONS: The combined chemotherapy and photothermal therapy of PC10A/DOX/HAuNS hydrogels could significantly improve the therapeutic effect. Therefore, the multifunctional hydrogel PC10A/DOX/HAuNS is promising to provide a new strategy for sustained chemo-photothermal therapy.

An injectable hybrid hydrogel based on a genetically engineered polypeptide for second near-infrared fluorescence/photoacoustic imaging-monitored sustained chemo-photothermal therapy.

An injectable multifunctional hydrogel based on an engineered coiled-coil polypeptide, Ag2S quantum dots (QDs), and paclitaxel (PTX) has been developed for sustained chemo-photothermal therapy. Oil-soluble Ag2S QDs and PTX were first loaded into nanogels formed with engineered polypeptide PC10A by ultrasonic treatment to prepare PC10A/Ag2S QD/PTX nanogels. The multifunctional PC10A/Ag2S QD/PTX hydrogels were prepared by dissolving the PC10A/Ag2S QD/PTX nanogels into the PC10A hydrogel. The PC10A/Ag2S QD/PTX hydrogel can be injected directly into the site of tumors. In vitro and in vivo toxicity results showed that the PC10A/Ag2S QD/PTX hydrogel presented excellent biocompatibility. Compared with single near-infrared photothermal therapy and chemotherapy, the combined therapy could effectively suppress the growth of SKOV3 ovarian carcinoma tumor. In addition, real-time monitoring of the in vivo degradation of the PC10A/Ag2S QD/PTX hydrogel was achieved by near-infrared fluorescence imaging and photoacoustic imaging. These results demonstrated that this injectable multifunctional PC10A/Ag2S QD/PTX hydrogel has the potential as a theranostic platform for sustained cancer treatments.

High quantum yield Ag2S quantum dot@polypeptide-engineered hybrid nanogels for targeted second near-infrared fluorescence/photoacoustic imaging and photothermal therapy.

A high quantum yield (4.3%) hybrid nanogel system based on engineered polypeptides and Ag2S quantum dots has been developed as a multifunctional diagnostic and therapeutic agent for targeted second near-infrared fluorescence, photoacoustic imaging, and photothermal therapy.

Polypeptide-Engineered Hydrogel Coated Gold Nanorods for Targeted Drug Delivery and Chemo-photothermal Therapy.

A new hybrid nanogel system using polypetide-engineered coated gold nanorods has been developed for targeted drug delivery and tumor chemo-photothermal therapy. A triblock engineered polypeptide PC10A(RGD) was immobilized on the surface of gold nanorods by the electrostatic adsorption. The immobilized PC10A(RGD) formed hydrogel by self-assembly to load doxorubicin for chemotherapy. Coating polypeptide-engineering hydrogel on gold nanorods enhanced the stability in high-salt media and significantly reduced the cytotoxicity. An arginine-glycine-aspartic acid motif was introduced into the polypeptide on the surface of hybrid nanogels to promote cellular uptake through receptor-mediated endocytosis in αvß3 overexpressing HeLa cells. In addition, compared with single chemotherapy and near-infrared photothermal therapy, the combination therapy has a synergistic effect on the cancer cells. Thus, the chemo-photothermal therapy based on polypeptide-engineered hydrogel coated gold nanorods and doxorubicin is expected to have great potential impact on cancer therapy.

A facile method to in situ fabricate three dimensional gold nanoparticle micropatterns in a cell-resistant hydrogel.

A facile method for in situ fabrication of three-dimensional gold nanoparticle micropatterns in a cell-resistant polyethylene glycol hydrogel has been developed by combining photochemical synthesis of gold nanoparticles with photolithography technology. The gold nanoparticle micropatterns were further bio-modified with cell integrated polypeptide NcysBRGD based on a gold-thiol bond to improve cell behaviors. Primary cell tests showed that NcysBRGD can enhance cell adhesion very well on the surface of gold nanoparticle micropatterns.

An engineered coiled-coil polypeptide assembled onto quantum dots for targeted cell imaging.

Quantum dot (QD)-polypeptide probes have been developed through the specific metal-affinity interaction between polypeptides appended with N-terminal polyhistidine sequences and CdSe/ZnS core-shell QDs. The size and charge of a QD-polypeptide can be tuned by using different coiled-coil polypeptides. Compared to glutathione-capped QDs (QD-GSH), QD-polypeptide probes showed an approximately two- to three-fold luminescence increase, and the luminescence increase was not obviously related to the charge of the polypeptide. QD-polypeptide probes with different charge have a great effect on nonspecific cellular uptake. QD-polypeptide probes with negative charge exhibited lower nonspecific cellular uptake in comparison to the QD-GSH, while positively charged QD-polypeptide probes presented higher cellular uptake than the QD-GSH. A targeted QD-ARGD probe can obviously increase targeted cellular uptake in α v ß 3 overexpressing HeLa cells compared to QD-A. In addition, QD-polypeptide probes showed lower in vitro cytotoxicity compared to the original QDs. These results demonstrate that these QD-polypeptide probes with high specific cellular uptake, high fluorescence intensity and low background noise are expected to have great potential applications in targeted cell imaging.

A near-infrared light-controlled system for reversible presentation of bioactive ligands using polypeptide-engineered functionalized gold nanorods.

A near-infrared light-controlled hybrid platform with polypeptide-engineered functionalized gold nanorods has been designed for reversible presentation of the immobilized ligands to cell surface receptors on the engineered materials.