Integrated combination delivery of IDO inhibitor and paclitaxel for cancer treatment

doi:10.5246/jcps.2021.01.001

Abstract

Abstract:

In order to realize the combination of chemotherapy and immunotherapy, a reduction-responsive paclitaxel (PTX) prodrug PEG-SS-PTX was synthesized and used as a carrier to encapsulate IDO inhibitor CY-1-4 for preparing PEG-SS-PTX/CY-1-4 NPs. PEG-SS-PTX/CY-1-4 NPs were evaluated by cytotoxicity, immunogenic cell death (ICD) induction ability and anti-tumor efficacy. Dynamic light scattering (DLS) results showed that the size of PEG-SS-PTX/CY-1-4 NPs was about 149 nm. In vitro experiments indicated that its cytotoxicity was in a concentration-dependent manner, and it induced the ICD of B16-F10 cells. In vivo studies in melanoma mouse model indicated that PEG-SS-PTX/CY-1-4 NPs significantly inhibited the tumor growth and reduced the expression of IDO in tumor tissues. Moreover, it increased the rate of CD8⁺ T cells in the spleen. In summary, PEG-SS-PTX/CY-1-4 NPs achieved good anti-tumor effects and reduced the dose of chemotherapy drugs, which was a safe and effective combined delivery system.

Key words: Chemotherapy, Immunotherapy, Combination drug delivery, Nano drug delivery system, IDO activity inhibition, Immunogenic cell death

Supporting:

Figure S1. The structure of CY-1-4. The molecular weight is 294.23 and the chemical formula is C₁₄H₆N₄O₄.

Figure S2. Quantified individual tumor volumes of different groups of mice after various treatments.

Figure S3. The routine blood test result including PLT, PCT, MO, GR, GR%, WBC, LY%, RBC, MCHC, PDW, MPV, MO%, MCV, MCH, RDW, HGB, and HCT. (^*P < 0.05, ^****P < 0.0001 vs. PBS, ^# P < 0.05, ^### P < 0.001 vs. PEG-SS-PTX/CY-1-4 NPs.)

Figure S4. H & E staining for hearts, livers, spleens, lungs and kidneys. Organs were harvested 2 days after last treatment. Nuclei and cytoplasm were stained by hematoxylin and eosin, respectively.

Dakuan Wang, Bo Peng, Mengmeng Qin, Minghui Li, Ge Song, Bing He, Hua Zhang, Wenbing Dai, Qiang Zhang, Xiangbao Meng, Huan Meng, Xueqing Wang. Integrated combination delivery of IDO inhibitor and paclitaxel for cancer treatment[J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(1): 1-16.

Figures/Tables 9

Table 1. Basic characterization of NPs (n = 3, means ± SD).

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