The complex construction within the oral cavity causes incomplete surgical resection of oral squamous cell carcinoma (OSCC) that may enhance the risk of recurrence and metastasis in the treatment. In situ forming injectable hydrogels with minimally invasive procedures, encapsulation stability and stimuli-responsive degradation have emerged as promising carriers for local drug delivery. In this study, doxorubicin (DOX) was first encapsulated in biodegradable poly(D,L-lactide)-poly(ethylene glycol)-poly(D,L-lactide) (PDLLA-PEG-PDLLA) micelles and then loaded into an in situ injectable hyaluronic acid (HA) hydrogel, which was cross-linked by a matrix metalloproteinase-2 (MMP-2)-responsive peptide (GCRDGPQGIWGQDRCG) through a Michael addition reaction. In vitro studies demonstrated that the HA hydrogel had a sensitive MMP-2-responsive drug release profile. Investigations including MTT, live-dead, apoptosis, and wound healing assays illustrated that DOX micelle-loaded HA hydrogels exhibited outstanding cytotoxicity against squamous carcinoma cells (SCC-15). Furthermore, by in vivo studies, we also proved that HA hydrogels degraded faster in the tumor site than in normal tissue, which led to a local sustained release of DOX-loaded micelles and tumor growth inhibition of oral squamous cell carcinoma (OSCC) without any damage to the organs. Therefore, this work provides a remarkable drug delivery platform for local chemotherapy and other applications.

The synthesis and application of nano doxorubicin-indocyanine green matrix metalloproteinase-responsive hydrogel in chemophototherapy for head and neck squamous cell carcinoma Huan-huan Wang,1,* Zhi-guang Fu,1,* Wei Li,2 Yun-xia Li,1 Li-sheng Zhao,1 Li Wen,1 Jian-jun Zhang,2 Ning Wen1 1Department of Stomatology, Chinese PLA General Hospital, Beijing 100853, China; 2College of Chemical Engineering, Beijing University of Chemical Technology, Beijing 100029, China *These authors contributed equally to this work Background: Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies, with high rates of mortality and morbidity worldwide. Owing to the special anatomical location of this tumor, an effective, minimally invasive treatment with low systemic toxicity is highly desirable. Hydrogels have shown great potential for tumor-targeting therapy, with excellent performance. However, there have been few reports on co-loading photosensitizers and chemotherapeutic drugs into hydrogels. In this study, we synthesized a nano doxorubicin-indocyanine green matrix metalloproteinase (MMP)-responsive hydrogel (denoted as NDIMH), combining chemotherapy and phototherapy, to achieve superior antitumor efficacy.Methods: First, NDIMH was synthesized and characterized by scanning electron microscopy and drug-release assays. Second, the photosensitivity properties and antitumor efficiency of this drug delivery system were studied in vivo and in vitro. Last, the imaging and biodistribution of NDIMH were monitored using the Maestro EX in vivo imaging system.Results: The nanodrugs loaded into the smart hydrogel exhibited uniform size distribution, excellent size stability, and a sustained release in the presence of MMP-2. NDIMH showed ideal photosensitivity characteristics under light. NDIMH with 808 nm near-infrared (NIR) irradiation effectively inhibited the viability, invasion, and metastasis of SCC-15 in vitro. After intratumoral injection of NDIMH with 808 nm NIR illumination, the hydrogels exhibited favorable synergistic antitumor efficacy and acceptable biosafety. Additionally, fluorescence imaging showed that NDIMH could significantly improve the retention of nanodrugs at the tumor site.Conclusion: The intratumoral injection of NDIMH with 808 nm NIR irradiation could be a promising chemophototherapy alternative for HNSCC. Keywords: hydrogel, MMP-responsive, doxorubicin, indocyanine green, chemophototherapy

GMSCs-Exo promote proliferation, migration, and tube formation of HUVECs by regulating the Wnt/β-catenin signalling pathway in a high-glucose environment. GMSCs-Exo were loaded and delivered via PHE microspheres, novel porous microscaffolds with superb biocompatibility.

Background: Corneal neovascularization (CoNV) threatens vision by disrupting corneal avascularity, however, current treatments, including pharmacotherapy and surgery, are hindered by limitations in efficacy and adverse effects. Minocycline, known for its anti-inflammatory properties, could suppress CoNV but faces challenges in effective delivery due to the cornea's unique structure. Therefore, in this study a novel drug delivery system using minocycline-loaded nano-hydroxyapatite/poly (lactic-co-glycolic acid) (nHAP/PLGA) nanoparticles was developed to improve treatment outcomes for CoNV. Results: Ultra-small nHAP was synthesized using high gravity technology, then encapsulated in PLGA by a double emulsion method to form nHAP/PLGA microspheres, attenuating the acidic by-products of PLGA degradation. The MINO@PLGA nanocomplex, featuring sustained release and permeation properties, demonstrated an efficient delivery system for minocycline that significantly inhibited the CoNV area in an alkali-burn model without exhibiting apparent cytotoxicity. On day 14, the in vivo microscope examination and ex vivo CD31 staining corroborated the inhibition of neovascularization, with the significantly smaller CoNV area (29.40% ± 6.55%) in the MINO@PLGA Tid group (three times daily) than that of the control group (86.81% ± 15.71%), the MINO group (72.42% ± 30.15%), and the PLGA group (86.87% ± 14.94%) (p < 0.05). Fluorescein sodium staining show MINO@PLGA treatments, administered once daily (Qd) and three times daily (Tid) demonstrated rapid corneal epithelial healing while the Alkali injury group and the DEX group showed longer healing times (p < 0.05). Additionally, compared to the control group, treatments with dexamethasone, MINO, and MINO@PLGA were associated with an increased expression of TGF-β as evidenced by immunofluorescence, while the levels of pro-inflammatory cytokines IL-1β and TNF-α demonstrated a significant decrease following alkali burn. Safety evaluations, including assessments of renal and hepatic biomarkers, along with H&E staining of major organs, revealed no significant cytotoxicity of the MINO@PLGA nanocomplex in vivo. Conclusions: The novel MINO@PLGA nanocomplex, comprising minocycline-loaded nHAP/PLGA microspheres, has shown a substantial capacity for preventing CoNV. This study confirms the complex's ability to downregulate inflammatory pathways, significantly reducing CoNV with minimal cytotoxicity and high biosafety in vivo. Given these findings, MINO@PLGA stands as a highly promising candidate for ocular conditions characterized by CoNV. Graphical