ReferenceID 5287
Local delivery of gambogic acid to improve anti-tumor immunity against oral squamous cell carcinoma
J Control Release
Oral squamous cell carcinoma (OSCC) accounts for nearly 90% of oral cavity malignancies. However, despite significant advances in the last four decades, little improvement has been achieved in the overall survival rates
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Record Fields
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- Reference Id
- 5287
- Evidence Id
- 21877
- Core Evidence Id
- 21877
- Source Reference Id
- 3835
- Herb2 Reference Id
- HBREF004632
- Subject Paper Key
- HBIN027097_36096364
- Pubmed Id
- 36096364
- Doi
- 10.1016/j.jconrel.2022.09.010
- Paper Title
- Local delivery of gambogic acid to improve anti-tumor immunity against oral squamous cell carcinoma
- Paper Abstract
- Oral squamous cell carcinoma (OSCC) accounts for nearly 90% of oral cavity malignancies. However, despite significant advances in the last four decades, little improvement has been achieved in the overall survival rates for OSCC patients. While gambogic acid (GA) is a potential candidate compound for treating a variety of malignancies, its anti-cancer impact on OSCC has not to be completely investigated. The tumor immune microenvironment (TIME) has been proven to play a crucial role in the prognosis of cancer patients. Although there are few reports on the T cell activation effect of GA, the regulation of GA on the TIME of OSCC has barely been studied yet. In this study, GA was applied to treat OSCC-bearing mice through in situ controlled release. First, GA-loaded mPEG 2000 -PCL micelles (GA-MIC) were prepared by the thin-film hydration method to improve the aqueous dispersibility of GA. Second, poly(D, l-lactide)-poly(ethylene glycol)-poly(D, l-lactide) (PLEL) was synthesized for thermosensitive hydrogel preparation. Third, GA-MIC was mixed with PLEL to form an injectable therapeutic hydrogel (GA-MIC-GEL). The anti-tumor and TIME regulation effects of GA-MIC-GEL on tumor-bearing mice were further examined. The results showed that the thermosensitive GA-MIC-GEL with sensitive sol-gel transition characteristics could form hydrogel at 37 °C within 24 s, facilitating the local delivery and sustained GA release. Biochemical, hematological, and pathological analysis proved that GA-MIC-GEL has good biological safety. Moreover, GA-MIC-GEL promoted an obvious regression of both primary and distant tumors on the OSCC mouse models. Mechanically, GA-MIC-GEL down-regulated the expression of PD-1, increased the frequency of cytotoxic T cells and reduced the immunosuppressive cellular components, which boosted the anti-tumor immunity of OSCC-bearing mice. The constructed thermosensitive hydrogel for local delivery of GA has provided a safe and effective strategy with great potential for OSCC therapy.
- Journal
- J Control Release
- Publish Year
- 2022
- Experiment Subject
- mouse; patient
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Malignancies; Tumor; Tumors; Oral Cavity Malignancies; Cancer; Oral Squamous Cell Carcinoma
- Paper Title Cn
- Paper Title En
- Local delivery of gambogic acid to improve anti-tumor immunity against oral squamous cell carcinoma
- Bilingual Status
- semi_complete