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用于结肠癌主动靶向的聚（d，l-丙交酯-乙交酯）表面锚定载生物素伊立替康纳米颗粒

Poly(d,l-lactide--glycolide) Surface-Anchored Biotin-Loaded Irinotecan Nanoparticles for Active Targeting of Colon Cancer.

作者信息

Giram Prabhanjan S, Nimma Ramakrishna, Bulbule Anuradha, Yadav Amit Singh, Gorain Mahadeo, Venkata Radharani Nalukurthi Naga, Kundu Gopal C, Garnaik Baijayantimala

机构信息

Polymer Science and Engineering Division, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, India.

Academy of Scientific and Innovative Research AcSIR Headquarters, CSIR-HRDC Campus Sector 19, Kamla Nehru Nagar, Ghaziabad, Uttar Pradesh 201 002, India.

出版信息

ACS Omega. 2024 Jan 10;9(3):3807-3826. doi: 10.1021/acsomega.3c07833. eCollection 2024 Jan 23.

DOI:10.1021/acsomega.3c07833
PMID:38284072
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10809773/
Abstract

A poly(d,l-lactide--glycolide) (PLGA) copolymer was synthesized using the ring-opening polymerization of d,l-lactide and glycolide monomers in the presence of zinc proline complex in bulk through the green route and was well characterized using attenuated total reflectance-Fourier transform infrared, H and C nuclear magnetic resonance, gel permeation chromatography, differential scanning calorimetry, X-ray diffraction, matrix-assisted laser desorption/ionization time-of-flight, etc. Furthermore, PLGA-conjugated biotin (PLGA-B) was synthesized using the synthesized PLGA and was employed to fabricate nanoparticles for irinotecan (Ir) delivery. These nanoparticles (PLGA-NP-Ir and PLGA-B-NP-Ir) were tested for physicochemical and biological characteristics. PLGA-B-NP-Ir exhibited a stronger cellular uptake and anticancer activity as compared to PLGA-NP-Ir in CT-26 cancer cells (log < 0.05). The accumulation and retention of fluorescence-labeled nanoparticles were observed to be better in CT-26-inoculated solid tumors in Balb/c mice. The PLGA-B-NP-Ir-treated group inhibited tumor growth significantly more (log < 0.001) than the untreated control, PLGA-NP-Ir, and Ir-treated groups. Furthermore, no body weight loss, hematological, and blood biochemical tests demonstrated the nanocarriers' nontoxic nature. This work presents the use of safe PLGA and the demonstration of a proof-of-concept of biotin surface attached PLGA nanoparticle-mediated active targeted Ir administration to combat colon cancer. To treat colon cancer, PLGA-B-NP-Ir performed better due to specific active tumor targeting and greater cellular uptake due to biotin.

摘要

通过绿色路线，在脯氨酸锌配合物存在下，由d，l-丙交酯和乙交酯单体本体开环聚合合成了聚（d，l-丙交酯-乙交酯）（PLGA）共聚物，并使用衰减全反射傅里叶变换红外光谱、氢和碳核磁共振、凝胶渗透色谱、差示扫描量热法、X射线衍射、基质辅助激光解吸/电离飞行时间等方法对其进行了充分表征。此外，使用合成的PLGA合成了PLGA共轭生物素（PLGA-B），并将其用于制备用于递送伊立替康（Ir）的纳米颗粒。对这些纳米颗粒（PLGA-NP-Ir和PLGA-B-NP-Ir）的物理化学和生物学特性进行了测试。在CT-26癌细胞中，与PLGA-NP-Ir相比，PLGA-B-NP-Ir表现出更强的细胞摄取和抗癌活性（log ＜0.05）。观察到荧光标记的纳米颗粒在Balb/c小鼠接种CT-26的实体瘤中的积累和保留更好。PLGA-B-NP-Ir治疗组比未治疗的对照组、PLGA-NP-Ir组和Ir治疗组更显著地抑制肿瘤生长（log ＜0.001）。此外，体重减轻、血液学和血液生化测试均未表明纳米载体具有毒性。这项工作展示了安全的PLGA的应用，并证明了生物素表面附着的PLGA纳米颗粒介导的活性靶向Ir给药对抗结肠癌的概念验证。由于生物素具有特异性的活性肿瘤靶向作用和更高的细胞摄取率，PLGA-B-NP-Ir在治疗结肠癌方面表现更佳。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d225/10809773/73d750374287/ao3c07833_0012.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d225/10809773/c84448bb51f8/ao3c07833_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d225/10809773/5687e85a0a78/ao3c07833_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d225/10809773/7f948528d424/ao3c07833_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d225/10809773/6c533ea718c2/ao3c07833_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d225/10809773/5795724a4d83/ao3c07833_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d225/10809773/c71771f3740f/ao3c07833_0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d225/10809773/71f245fefb34/ao3c07833_0010.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d225/10809773/73d750374287/ao3c07833_0012.jpg

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