Sustained co-delivery of gemcitabine and cis-platinum via biodegradable thermo-sensitive hydrogel for synergistic combination therapy of pancreatic cancer

Pancreatic cancer is one of the most devastating cancers with poor prognosis and no significant change in the survival rate over the past decades.Localized targeted drug delivery through interventional endoscopic ultrasonography-guided fine-needle injection (EUS-FNI) is an attractive and minimally invasive strategy for inoperable pancreatic cancer.An injectable in-situ formed long-lasting drug delivery system is a promising alternative for the localized treatment of pancreatic cancer via EUS-FNI.Here,a biodegradable thermo-sensitive copolymer hydrogel for the co-delivery of anticancer agents gemcitabine (GEM) and cis-platinum (DDP) was developed.This hydrogel is a free flowable liquid at room temperature that changes into a semi-solid hydrogel following injection in response to the physiological temperature.Both in vitro and in vivo drug release behaviors indicate sustained drug release of this delivery system.Synergistic cellular proliferation inhibition and desirable apoptosis promotion have been found when pancreatic cancer Bxpc-3 cells were co-cultured with this GEM-DDP/hydrogel system.After a single intratumoral injection,the dual-drug loaded hydrogel formulation exhibited superior anti-tumor efficacy and minimized systemic side effect on pancreatic cancer xenograft mouse model in comparison to the intravenously injected free GEM and DDP combination.In addition,a strong synergistic therapeutic effect of the GEM-DDP/hydrogel system against pancreatic cancer has been found in vitro and in vivo compared to the single-drug loaded hydrogel composites.The obtained findings suggest this developed thermo-sensitive copolymer hydrogel system as a potential universal carrier for the localized targeted delivery of multi-drugs,for use in a variety of inoperable solid tumors.

Gold nanorods and nanohydroxyapatite hybrid hydrogel for preventing bone tumor recurrence via postoperative photothermal therapy and bone regeneration promotion

Osteosarcoma is a malignant bone tumor,which often occurs in adolescents.However,surgical resection usually fails to completely remove the tumor clinically,which has been the main cause of postoperative recurrence and metastasis,resulting in the high death rate of patients.At the same time,osteosarcoma invades a large area of the bone defect,which cannot be self-repaired and seriously affects the life quality of the patients.Herein,a bifunctional methacrylated gelatin/methacrylated chondroitin sulfate hydrogel hybrid gold nanorods(GNRs)and nanohydroxyapatite(nHA),which possessed excellent photothermal effect,was constructed to eradicate residual tumor after surgery and bone regeneration.In vitro,K7M2wt cells(a mouse bone tumor cell line)can be efficiently eradicated by photothermal therapy of the hybrid hydrogel.Meanwhile,the hydrogel mimics the extracellular matrix to promote proliferation and osteogenic differentiation of mesenchymal stem cells.The GNRs/nHA hybrid hydrogel was capable of photothermal treatment of postoperative tumors and bone defect repair in a mice model of tibia osteosarcoma.Therefore,the hybrid hydrogel possesses dual functions of tumor therapy and bone regeneration,which shows great potential in curing bone tumors and provides a new hope for tumor-related bone complex disease.

Mesoporous PtPd nanoparticles for ligand-mediated and imaging-guided chemo-photothermal therapy of breast cancer

The synergistic therapy of chemotherapy and photothermal therapy(PTT)has been reported as a promising antitumor strategy.To achieve effective combination therapy,developing more suitable candidate nanomaterials with optimal photothermal property and high chemical drug loading capacity is very necessary.Herein,a bimetallic PtPd nanoparticle was synthesized with the merits of excellent photothermal effect and mesoporous structure for doxorubicin(DOX)loading.We further designed PtPd-ethylene glycol(PEG)-folic acid(FA)-doxorubicin(DOX)nanoparticle for chemo-photothermal therapy of MCF-7 tumor with folic acid engineering to achieve active targeting.Moreover,excellent photoacoustic(PA)imaging of PtPd-PEG-FA-DOX nanoparticles facilitated the precise in vivo tracking and further evaluation of nanoparticles’targeting effect.The in vitro and in vivo results both demonstrated PtPd-PEG-FA-DOX nanoparticles serve as a safe and promising system for effective treatment of MCF-7 tumor.

Camptothecin@HMSNs/thermosensitive hydrogel composite for applications in preventing local breast cancer recurrence

Camptothecin has a strong tumor killing ability for a variety of tumor cells with its special anti-cancer mechanism including the breast cancer. However, because of its infinite hydrophobic property, its clinical application has been greatly limited. Early prevention of loco regional recurrence for the breast cancer is critical for patients who have undergone breast-conserving therapy. In the study,CPT was used for the inhibition of the recurrence after the operation. The hollow mesoporous silica nanoparticles were used as the carrier to improve the hydrophilic property and increase its bioavailability with the high loading capacity. The ability of the cellular uptake and antitumor activity was increased. Hydrogel was the ideal carrier for local therapy, so the CPT@HMSNs were loaded into the PLEL thermo sensitive hydrogel to be injected into the tumor sites after the tumor was resected. The recurrence was reduced in the group of CPT-HMSNs-PLEL and the side effect of CPT was decreased. They exhibit distinguished potential as drug carrier for local delivery.

Cyclophosphamide loaded thermo-responsive hydrogel system synergize with a hydrogel cancer vaccine to amplify cancer immunotherapy in a prime-boost manner

Although neoantigen-based cancer vaccines show great potential in cancer immunotherapy due to their ability to induce effective and long-lasting anti-tumor immunity,their development is hindered by the limitations of neoantigens identification,low immunogenicity,and weak immune response.Cyclophosphamide(CTX)not only directly kills tumors but also causes immunogenic cell death,providing a promising source of antigens for cancer vaccines.Herein,a combined immunotherapy strategy based on temperature-sensitive PLEL hydrogel is designed.First,CTX-loaded hydrogel is injected intratumorally into CT26 bearing mice to prime anti-tumor immunity,and then 3 days later,PLEL hydrogels loaded with CpG and tumor lysates are subcutaneously injected into both groins to further promote anti-tumor immune responses.The results confirm that this combined strategy reduces the toxicity of CTX,and produces the cytotoxic T lymphocyte response to effectively inhibit tumor growth,prolong survival,and significantly improve the tumor cure rate.Moreover,a long-lasting immune memory response is observed in the mice.About 90%of the cured mice survive for at least 60 days after being re-inoculated with tumors,and the distant tumor growth is also well inhibited.Hence,this PLEL-based combination therapy may provide a promising reference for the clinical promotion of chemotherapy combined with cancer vaccines.

Ag2S nanoparticles as an emerging single-component theranostic agent

Last two decades,with the rapid changes and development of nanotechnology and biological materials,diverse multi-functional nanomaterials emerging,which offers a novel way to treat and diagnose diseases,and therefore spawned the new biomedical technology of theranostics,which integrates the treatment and diagnosis or monitoring of diseases into one.Ag2S as a bio-nanomaterial with low biotoxicity has attracted more and more attention due to its good photoluminescence properties and fluorescence imaging of small animals in the second near-infrared region(NIR-Ⅱ).Meanwhile,Ag2S has the ability to absorb near-infrared light strongly because of its local surface plasma resonance(LSPR)effect and had become a kind of photothermal conve rters with good photothermal conve rsion efficiency.More interestingly,both photothermal effect and fluorescence characteristics of Ag2S nanoparticles(NPs)are closely related to their particle sizes.However,the relationship between photothermal effect and fluorescence characteristics of Ag2S NPs and their sizes has not been reviewed so far.Herein,the synthesis methods and influencing factors of synthesize Ag2S NPs with different sizes were compared firstly,and then the photothermal effect and fluorescence characte ristics of Ag2S NPs with different sizes were summarized.Finally,the possibilities and challenges of using Ag2S NPs to construct theranostic agent were discussed in the end.