Antitumor Activity of α-Linolenic Acid-Paclitaxel Conjugate Nanoparticles: In vitro and in vivo

Abstract

Purpose: Small molecule modified antitumor drug conjugate nanoparticles have the advantages of high drug loading, simple synthesis and preparation, and better biocompatibility. Due to the large demand for exogenous α-linolenic acid (ALA) by tumor cells, we synthesized α-linolenic acid-paclitaxel conjugate (ALA-PTX) and prepared α-linolenic acidpaclitaxel conjugate nanoparticles (ALA-PTX NPs), in order to obtain better tumor cellular uptake and antitumor activity in vitro and in vivo. Methods: We synthesized and characterized ALA-PTX, and then prepared and characterized ALA-PTX NPs. The cellular uptake, uptake pathways, intracellular behavior, in vitro and in vivo antitumor activity of ALA-PTX NPs were evaluated. Results:The size of ALA-PTX NPs was approximately 110.7±1.7 nm. The drug loading was approximately 90% (w/w) with CrEL-free and organic solvent-free characteristics. The cellular uptake of ALA-PTX NPs was significantly higher than that of PTX injection by MCF-7, MCF-7/ADR and HepG2 cells. In these three cell lines, the cellular uptake of ALA-PTX NPs at 6h was approximately 1.5-2.6 times higher than that of PTX injection. ALA-PTX NPs were ingested through clathrin-mediated endocytosis, then transferred to lysosomes, and could dissolve in cells to play an antitumor activity. The in vitro and in vivo antitumor activity of ALA-PTX NPs was confirmed in MCF-7/ADR and HepG2 cell models and tumor-bearing nude mouse models. Conclusion: ALA-PTX NPs developed in our study could provide a new method for the preparation of nano-delivery systems suitable for antitumor therapy that could increase tumor cellular uptake and enhance antitumor activity.

Antitumor Activity of the Zinc Oxide Nanoparticles Coated with Low-Molecular-Weight Heparin and Doxorubicin Complex In Vitro and In Vivo

“…The in vitro antitumor activity of ZnO-LD NPs was investigated in PC-3M and 4T1 cell lines using the SRB method, as previously reported. , Briefly, PC-3M cells and 4T1 cells were seeded in 96-well plates (8 × 10 3 cells/well) and incubated at 37 °C for 24 h. Then, cells were cultured with different concentrations of ZnO-LD NPs for 48 h. The cell viability was determined using SRB, which allowed quantification of the living cells by measuring absorbance at 540 nm by a 96-well plate reader (Elx808). The IC 50 values were calculated using dose–effect curves.…”

Integrating Traditional Machine Learning and Deep Learning for Precision Screening of Anticancer Peptides: A Novel Approach for Efficient Drug Discovery

“…The purity of the synthetic peptide was detected by high-performance liquid chromatography (HPLC) to be more than 95%. The in vitro cytotoxicity of peptides was evaluated in 4T1 cells (mouse breast cancer cells) using the sulfonyl rhodamine B (SRB) assay (Sigma-Aldrich, St. Louis, MO, USA). , 4T1 cells (6 × 10 3 cells/well) were seeded in 96-well plates, incubated for 24 h, and then treated with peptides at 37 °C for 24 h. The cell viability was determined using SRB, which allowed quantification of the living cells by measuring absorbance at 540 nm with a 96-well plate reader (model 680; Bio-Rad Laboratories Inc., Hercules, CA, USA). The half-maximal inhibitory concentration (IC50) was calculated according to the dose–effect curves using GraphPad Prism 8 software.…”

Disulfide Bond-Based SN38 Prodrug Nanoassemblies with High Drug Loading and Reduction-Triggered Drug Release for Pancreatic Cancer Therapy

“…The SRB method was utilized to investigate the cytotoxicity of SNSS NAs in relation to the human pancreatic carcinoma cell lines Panc-1 and BxPC-3. 34 , 42 Briefly, cells were seeded in 96-well plates at a density of 2×10 3 cells/well and incubated for 24 h. The cells were then treated with different concentrations of SNSS NAs, CPT-11, and SN38, respectively. The cells were washed, fixed, and stained with SRB after being exposed to an incubation period of 72 h. Then 10 mM Tris buffer was added, and the OD value of each well was measured at 540 nm using a microplate reader (BioTek Synergy HTX, BioTek Instruments, Inc., Winooski, VT, USA).…”