Folate Receptor-Targeted Camptothecin-Loaded PLGA-Glutenin Nanoparticles for Effective Breast cancer Treatment

IF 4.7 3区 工程技术 Q2 ENGINEERING, ENVIRONMENTAL Journal of Polymers and the Environment Pub Date : 2024-09-03 DOI:10.1007/s10924-024-03391-6
Raja Rajeswari Rajeshkumar, Theivendren Panneerselvam, Parasuraman Pavadai, Sureshbabu Ram Kumar Pandian, Alagarsamy Santhana Krishna Kumar, Murugesan Sankaranarayan, Shanmugampillai Jeyarajaguru Kabilan, Selvaraj Kunjiappan
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Abstract

The combination of natural and synthetic polymers for nanomedicine development had many advantages, including less toxicity, biocompatibility, prolonged circulation, higher stability, and ease of surface modification. Here, a novel folic acid-conjugated Camptothecin-loaded-poly (lactic-co-glycolic) acid-glutenin nanoparticles (FA-CPT-PLGA-Glu NPs) was fabricated to treat breast cancer. FA-CPT-PLGA-Glu NPs target breast cancer cells via upregulated folate receptors and delivered their toxic payloads without disrupting healthy cells. First, CPT-loaded PLGA NPs were created using a modified emulsification/evaporation technique. Second, Glu-based CPT-PLGA NPs were synthesized using a layer-by-layer assembly, and their physiochemical properties were validated. CPT encapsulation efficiency and loading capacity into PLGA-Glu NPs were 74.95 ± 1.34% and 4.78 ± 1.08%, respectively. CPT-PLGA-Glu NPs exhibited sustained and controlled release of loaded-CPT from NPs, and the highest content was released in an acidic environment (pH 5.3), which will be advantageous for cancer treatment. Later, FA-CPT-PLGA-Glu NPs were synthesized by simple conjugation chemistry. The fabricated FA-CPT-PLGA-Glu NPs were around 100 nm in size, with a spherical form and crystalline nature. FA-CPT-PLGA-Glu NPs show strong cytotoxicity activity, and its IC50 value was 16.33 µg × mL− 1 against breast cancer cell line (MCF-7). This folate-receptor-targeted NPs are more effectively internalized into MCF-7 cells, causing ROS generation, cell growth inhibition, and apoptosis. The activity of caspase-3 and − 9 causes MCF-7 cells apoptosis by internalized CPT. Further, internalized CPT induces potential loss of mitochondrial transmembrane and damages the nuclear integrity of the cancer cells. These results showed that the FA-CPT-PLGA-Glu NPs target upregulated folate receptors on the surface of MCF-7 cells.

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用于有效治疗乳腺癌的叶酸受体靶向喜树碱负载型 PLGA 谷登素纳米粒子
将天然聚合物和合成聚合物结合起来开发纳米药物具有许多优点,包括毒性低、生物相容性好、可延长循环时间、稳定性高以及易于表面修饰。本文制备了一种新型叶酸共轭喜树碱负载聚(乳酸-聚甘醇酸)-谷氨酰胺纳米粒子(FA-CPT-PLGA-Glu NPs),用于治疗乳腺癌。FA-CPT-PLGA-Glu NPs 通过上调的叶酸受体靶向乳腺癌细胞,并在不破坏健康细胞的情况下释放其毒性载荷。首先,使用改良的乳化/蒸发技术制备出了载CPT的PLGA NPs。其次,采用逐层组装法合成了基于 Glu 的 CPT-PLGA NPs,并验证了它们的理化性质。CPT 在 PLGA-Glu NPs 中的包封效率和负载能力分别为 74.95 ± 1.34% 和 4.78 ± 1.08%。CPT-PLGA-Glu NPs表现出负载CPT从NPs中的持续和可控释放,并且在酸性环境(pH 5.3)中释放的含量最高,这将有利于癌症治疗。随后,通过简单的共轭化学反应合成了FA-CPT-PLGA-Glu NPs。合成的 FA-CPT-PLGA-Glu NPs 大小约为 100 nm,呈球形,具有结晶性。FA-CPT-PLGA-Glu NPs 具有很强的细胞毒性活性,其对乳腺癌细胞株(MCF-7)的 IC50 值为 16.33 µg × mL-1。这种叶酸受体靶向 NPs 能更有效地被 MCF-7 细胞内化,导致 ROS 生成、细胞生长抑制和细胞凋亡。内化的叶酸受体靶向 NPs 能更有效地内化 MCF-7 细胞,导致 ROS 生成、细胞生长抑制和细胞凋亡。此外,内化的 CPT 会诱导线粒体跨膜的潜在损失,并破坏癌细胞核的完整性。这些结果表明,FA-CPT-PLGA-Glu NPs 可靶向 MCF-7 细胞表面上调的叶酸受体。
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来源期刊
Journal of Polymers and the Environment
Journal of Polymers and the Environment 工程技术-高分子科学
CiteScore
9.50
自引率
7.50%
发文量
297
审稿时长
9 months
期刊介绍: The Journal of Polymers and the Environment fills the need for an international forum in this diverse and rapidly expanding field. The journal serves a crucial role for the publication of information from a wide range of disciplines and is a central outlet for the publication of high-quality peer-reviewed original papers, review articles and short communications. The journal is intentionally interdisciplinary in regard to contributions and covers the following subjects - polymers, environmentally degradable polymers, and degradation pathways: biological, photochemical, oxidative and hydrolytic; new environmental materials: derived by chemical and biosynthetic routes; environmental blends and composites; developments in processing and reactive processing of environmental polymers; characterization of environmental materials: mechanical, physical, thermal, rheological, morphological, and others; recyclable polymers and plastics recycling environmental testing: in-laboratory simulations, outdoor exposures, and standardization of methodologies; environmental fate: end products and intermediates of biodegradation; microbiology and enzymology of polymer biodegradation; solid-waste management and public legislation specific to environmental polymers; and other related topics.
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