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In-vivo Anticancer Efficacy of Self-Targeted Methotrexate-Loaded Polymeric Nanoparticles in Solid Tumor-Bearing Rat.

International immunopharmacology(2023)

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摘要
Here, cytotoxicity and antitumor efficacy against a chemically (N-methyl-N-nitrosourea) generated mammary tumor in rats were assessed using methotrexate-loaded chitosan nanoparticles (Meth-Cs-NPs). Meth-Cs-NPs intravenous administrated resulted in noticeably decreased tumor incidence, multiplicity, and weight. Further, kidney function tests for the treated groups resulted in noticeably decreased ALP (Meth-Cs-NPs; 244 +/- 15, diseases control; 403 +/- 14 U/L), Creatinine (Meth-Cs-NPs; 0.81 +/- 0.05, diseases control; 2 +/- 0.05 mg/dl), and Urea (Meth-Cs-NPs; 56.62 +/- 5, diseases control; 113 +/- 6 mg/dl) levels, close to a normal control group. Simi-larly, liver function tests showed significantly decreased serum biomarkers, SGPT (Meth-Cs-NPs; 40 +/- 1.8, diseases control; 84 +/- 1.9 U/L) and SGOT (Meth-Cs-NPs; 15 +/- 2, diseases control; 55 +/- 4 U/L) levels in treated groups as compared to the untreated group (diseases control). From the results, pro-inflammatory cytokines were also markedly reduced in the treated group such as, TNF-alpha (Meth-Cs-NPs; 17.31 +/- 1.15, diseases control; 36.9 +/- 5 pg/mL), IL-113 (Meth-Cs-NPs; 433.3 +/- 66.5, diseases control; 1540 +/- 131.1 pg/mL), and IL-6 (Meth-Cs-NPs; 1515 +/- 53, diseases control; 2200.6 +/- 69 pg/mL) levels. Whereas Meth-Cs-NPs not only helped in lowering tumor multiplicity rates but also decrease inflammation. The studies could be successfully performed in chem-ically induced mammary tumors due to their easy, quick tumor growth and low mortality rates in rat models. According to the current study, Meth-Cs-NPs have high treatment potency and represent a possible therapeutic alternative for breast cancer treatment.
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关键词
Breast cancer,Nanoparticles,Biochemical analysis,ELISA assay,Histopathology
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