Concomitant Delivery of Pirarubicin and Salinomycin Synergistically Enhanced the Efficacy of Cancer Therapy and Reduced the Risk of Cancer Relapse

IF 3.4 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Mohd Anees, Priya Gupta, Harshdeep Kaur, Surender Kharbanda, Harpal Singh
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Abstract

Pirarubicin attracted considerable attention in clinical studies because of its high therapeutic efficacy and reduced toxicity in comparison with other anthracyclines. Nevertheless, ~ 30% patients undergoing PIRA treatment still experience relapse and metastasis. Clinical advancements unveiled that cancer stem cells (CSCs) residing in the tumor constitutes a major factor for such limitations and subsequently are the reason for treatment failure. Consequently, eradicating CSCs alongside bulk tumor is a crucial undertaking to attain utmost therapeutic efficacy of the treatment. Nevertheless, majority of the CSCs inhibitors currently under examination lack specificity, show unsynchronized bioavailability with other primary treatments and exhibit notable toxicity in their therapeutic applications, which is primarily attributable to their inadequate tumor-targeting capabilities. Therefore, we have developed a biodegradable polylactic acid based blend block copolymeric NPs for concomitant delivery of CSCs inhibitor Salinomycin (SAL) & chemotherapeutic drug Pirarubicin (PIRA) with an aim to improve the efficacy of treatment and prevent cancer relapse. Prepared NPs showed < 100 nm size and excellent loading with sustained release for both the drugs. Also, PIRA:SAL co-loaded NPs exhibits synergistically enhanced cytotoxicity against cancer cell as well as CSCs. Most importantly, NPs mediated co-delivery of the drugs showed complete tumor eradication, without any reoccurrence throughout the surveillance period. Additionally, NPs treatment didn’t show any histopathological alteration in vital organs confirming their non-toxic nature. Altogether, present study concludes that the developed PIRA:SAL NPs have excellent efficacy for tumor regression as well as prevention of cancer relapse, hence can be used as a potential combination therapy for cancer treatment.

Graphical abstract

Abstract Image

吡柔比星和盐霉素同时给药可协同增强癌症疗效并降低癌症复发风险
与其他蒽环类药物相比,吡柔比星具有疗效高、毒性低的特点,因此在临床研究中备受关注。然而,约 30% 接受 PIRA 治疗的患者仍会出现复发和转移。临床研究发现,肿瘤中的癌症干细胞(CSCs)是造成这种限制的主要因素,也是治疗失败的原因。因此,要获得最佳疗效,根除肿瘤干细胞是一项至关重要的工作。然而,目前研究的大多数 CSCs 抑制剂缺乏特异性,生物利用度与其他主要治疗方法不同步,在治疗应用中表现出明显的毒性,这主要归因于它们的肿瘤靶向能力不足。因此,我们开发了一种可生物降解的聚乳酸基混合嵌段共聚物 NPs,用于同时递送 CSCs 抑制剂 Salinomycin (SAL) 和化疗药物 Pirarubicin (PIRA),以提高疗效并防止癌症复发。制备的 NPs 显示
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来源期刊
AAPS PharmSciTech
AAPS PharmSciTech 医学-药学
CiteScore
6.80
自引率
3.00%
发文量
264
审稿时长
2.4 months
期刊介绍: AAPS PharmSciTech is a peer-reviewed, online-only journal committed to serving those pharmaceutical scientists and engineers interested in the research, development, and evaluation of pharmaceutical dosage forms and delivery systems, including drugs derived from biotechnology and the manufacturing science pertaining to the commercialization of such dosage forms. Because of its electronic nature, AAPS PharmSciTech aspires to utilize evolving electronic technology to enable faster and diverse mechanisms of information delivery to its readership. Submission of uninvited expert reviews and research articles are welcomed.
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