Antitumor activity of the bioreductive prodrug 3-(2-nitrophenyl) propionic acid-paclitaxel nanoparticles (NPPA-PTX NPs) on MDA-MB-231 cells: in vitro and in vivo

Duan, Xiao-Chuan; Yao, Xin; Zhang, Shuang; Xu, Meiqi; Hao, Yanli; Li, Zhantao; Zheng, Xiu-Chai; Liu, Man; Li, Zhuoyue; Li, Hui; Wang, Jingru; Feng, Zhen-Han; Zhang, Xuan

doi:10.2147/ijn.s186556

Cited by 7 publications

(7 citation statements)

References 30 publications

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“…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).…”

Section: Methodsmentioning

confidence: 99%

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

Zhong¹,

Li²,

Liu³

et al. 2023

IJN

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Purpose Chemotherapy is a significant and effective therapeutic strategy that is frequently utilized in the treatment of cancer. Small molecular prodrug-based nanoassemblies (SMPDNAs) combine the benefits of both prodrugs and nanomedicine into a single nanoassembly with high drug loading, increased stability, and improved biocompatibility. Methods In this study, a disulfide bond inserted 7-ethyl-10-hydroxycamptothecin (SN38) prodrug was rationally designed and then used to prepare nanoassemblies (SNSS NAs) that were selectively activated by rich glutathione (GSH) in the tumor site. The characterization of SNSS NAs and the in vitro and in vivo evaluation of their antitumor effect on a pancreatic cancer model were performed. Results In vitro findings demonstrated that SNSS NAs exhibited GSH-induced SN38 release and cytotoxicity. SNSS NAs have demonstrated a passive targeting effect on tumor tissues, a superior antitumor effect compared to irinotecan (CPT-11), and satisfactory biocompatibility with double dosage treatment. Conclusion The SNSS NAs developed in this study provide a new method for the preparation of SN38-based nano-delivery systems with improved antitumor effect and biosafety.

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Section: Methodsmentioning

confidence: 99%

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

Zhong¹,

Li²,

Liu³

et al. 2023

IJN

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“…The synthesis of NPPA-PTX (Supplementary Scheme 1) and the preparation of NPPA-PTX NPs were reported in our previous work (Song et al, 2016;Duan et al, 2019). NPPA-PTX-FAM was synthesized through click reaction by alkynylation modified NPPA-PTX and 6-FAM-Azid (Supplementary Schemes 2 and 3), and NPPA-PTX-FAM NPs were prepared by the same formulation as the previous research (Duan et al, 2019). Particle size and zeta potential were determined by dynamic light scattering (DLS) measurements (Malvern Zetasizer Nano ZS90, Malvern, UK).…”

Section: Preparation and Characterization Of Nppa-ptx Nanoparticlesmentioning

confidence: 99%

“…The prodrug nanomedicine based on the molecular selfassembly of amphiphilic prodrugs was developed in decades due to their higher loading efficiency and enhanced therapeutic efficiency (Li et al, 2019). In previous research (Song et al, 2016;Duan et al, 2019), PTX was conjugated with 3-(2-nitrophenyl) propionic acid (NPPA) to obtain a novel bioreductive PTX prodrug (NPPA-PTX). The results indicated that NPPA-PTX could completely convert to active PTX in tumor tissues and produce anti-tumor activity.…”

Section: Introductionmentioning

confidence: 99%

The synergistic antitumor activity of 3-(2-nitrophenyl) propionic acid-paclitaxel nanoparticles (NPPA-PTX NPs) and anti-PD-L1 antibody inducing immunogenic cell death

et al. 2021

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Cancer immunotherapy is a strategy that is moving to the frontier of cancer treatment in the current decade. In this study, we show evidence that 3-(2-nitrophenyl) propionic acid-paclitaxel nanoparticles (NPPA-PTX NPs), act as immunogenic cell death (ICD) inducers, stimulating an antitumor response which results in synergistic antitumor activity by combining anti-PD-L1 antibody (aPD-L1) in vivo. To investigate the antitumor immunity induced by NPPA-PTX NPs, the expression of both ICD marker calreticulin (CRT) and high mobility group box 1 (HMGB1) were analyzed. In addition, the antitumor activity of NPPA-PTX NPs combined with aPD-L1 in vivo was also investigated. The immune response was also measured through quantitation of the infiltration of T cells and the secretion of pro-inflammatory cytokines. The results demonstrate that NPPA-PTX NPs induce ICD of MDA-MB-231 and 4T1 cells through upregulation of CRT and HMGB1, reactivating the antitumor immunity via recruitment of infiltrating CD3þ, CD4þ, CD8þ T cells, secreting IFN-c, TNF-a, and the enhanced antitumor activity by combining with aPD-L1. These data suggest that the combined therapy has a synergistic antitumor activity and has the potential to be developed into a novel therapeutic regimen for cancer patients.

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“…ALA-PTX NPs were prepared using a simple precipitation method. 16,25,26 In brief, ALA-PTX and DSPE-PEG (ALA-PTX: DSPE-PEG = 1: 0.1, w/w) were dissolved in DMSO. A volume of 1 mL of the above solution was added dropwise into distilled water (3 mL) with stirring (300-500 rpm) at room temperature.…”

Section: Preparation Of Ala-ptx Npsmentioning

confidence: 99%

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

Xu¹,

Hao²,

Wang³

et al. 2021

IJN

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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.

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Antitumor activity of the bioreductive prodrug 3-(2-nitrophenyl) propionic acid-paclitaxel nanoparticles (NPPA-PTX NPs) on MDA-MB-231 cells: in vitro and in vivo

Cited by 7 publications

References 30 publications

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

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

The synergistic antitumor activity of 3-(2-nitrophenyl) propionic acid-paclitaxel nanoparticles (NPPA-PTX NPs) and anti-PD-L1 antibody inducing immunogenic cell death

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

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