scholarly journals A Self-Assembling Amphiphilic Peptide Dendrimer-Based Drug Delivery System for Cancer Therapy

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1092
Author(s):  
Dandan Zhu ◽  
Huanle Zhang ◽  
Yuanzheng Huang ◽  
Baoping Lian ◽  
Chi Ma ◽  
...  

Despite being a mainstay of clinical cancer treatment, chemotherapy is limited by its severe side effects and inherent or acquired drug resistance. Nanotechnology-based drug-delivery systems are widely expected to bring new hope for cancer therapy. These systems exploit the ability of nanomaterials to accumulate and deliver anticancer drugs at the tumor site via the enhanced permeability and retention effect. Here, we established a novel drug-delivery nanosystem based on amphiphilic peptide dendrimers (AmPDs) composed of a hydrophobic alkyl chain and a hydrophilic polylysine dendron with different generations (AmPD KK2 and AmPD KK2K4). These AmPDs assembled into nanoassemblies for efficient encapsulation of the anti-cancer drug doxorubicin (DOX). The AmPDs/DOX nanoformulations improved the intracellular uptake and accumulation of DOX in drug-resistant breast cancer cells and increased permeation in 3D multicellular tumor spheroids in comparison with free DOX. Thus, they exerted effective anticancer activity while circumventing drug resistance in 2D and 3D breast cancer models. Interestingly, AmPD KK2 bearing a smaller peptide dendron encapsulated DOX to form more stable nanoparticles than AmPD KK2K4 bearing a larger peptide dendron, resulting in better cellular uptake, penetration, and anti-proliferative activity. This may be because AmPD KK2 maintains a better balance between hydrophobicity and hydrophilicity to achieve optimal self-assembly, thereby facilitating more stable drug encapsulation and efficient drug release. Together, our study provides a promising perspective on the design of the safe and efficient cancer drug-delivery nanosystems based on the self-assembling amphiphilic peptide dendrimer.

2015 ◽  
Vol 112 (10) ◽  
pp. 2978-2983 ◽  
Author(s):  
Tuo Wei ◽  
Chao Chen ◽  
Juan Liu ◽  
Cheng Liu ◽  
Paola Posocco ◽  
...  

Drug resistance and toxicity constitute challenging hurdles for cancer therapy. The application of nanotechnology for anticancer drug delivery is expected to address these issues and bring new hope for cancer treatment. In this context, we established an original nanomicellar drug delivery system based on an amphiphilic dendrimer (AmDM), which could generate supramolecular micelles to effectively encapsulate the anticancer drug doxorubicin (DOX) with high drug-loading capacity (>40%), thanks to the unique dendritic structure creating large void space for drug accommodation. The resulting AmDM/DOX nanomicelles were able to enhance drug potency and combat doxorubicin resistance in breast cancer models by significantly enhancing cellular uptake while considerably decreasing efflux of the drug. In addition, the AmDM/DOX nanoparticles abolished significantly the toxicity related to the free drug. Collectively, our studies demonstrate that the drug delivery system based on nanomicelles formed with the self-assembling amphiphilic dendrimer constitutes a promising and effective drug carrier in cancer therapy.


2019 ◽  
Vol 73 ◽  
pp. 508-515 ◽  
Author(s):  
Alicja Zajdel ◽  
Daniel Wolny ◽  
Magdalena Kałucka-Janik ◽  
Adam Wilczok

Despite significant progress in the last few decades in breast cancer biology and the use of different therapeutic strategies, this cancer remains a serious clinical problem. Paclitaxel (PTX) is used to treat breast cancer both as a monotherapy and in combination with other anticancer drugs depending on the severity of the cancer, the presence of metastases and previous therapeutic management. It is characterized by high effectiveness both in early breast cancer and in metastatic breast cancer. Primary or acquired drug resistance of tumour cells to taxanes is a significant clinical problem in the treatment of various histological types of breast cancer. The main problem of resistance of tumour cells is the complexity and multifactorial nature of this phenomenon, which is conditioned by numerous different mechanisms that interact with each other. Among the known mechanisms of breast cancer cells resistance to PTX, the most important are the active removal of the drug from the cell related to the increased activity of ABC family membrane transporters, enhanced drug detoxification by cytochrome P450, CYP3A4/5 and CYP2C8 enzymes, changes within the molecular targets of PTX, microtubule and disorders of microtubule associated protein (MAPs) or apoptosis. This paper presents the latest reports on the mechanisms of drug resistance of breast cancer cells to PTX, pointing to modern strategies to counteract this adverse phenomenon.


2017 ◽  
Vol 8 (40) ◽  
pp. 6289-6299 ◽  
Author(s):  
Manuela Callari ◽  
Sandy Wong ◽  
Hongxu Lu ◽  
Janice Aldrich-Wright ◽  
Paul de Souza ◽  
...  

Co-delivery of two drugs in one nanoparticle is increasingly used to overcome, for example, multi-drug resistance in cancer therapy and therefore suitable drug carriers need to be developed.


2020 ◽  
Vol 13 ◽  
Author(s):  
Selin Yılmaz ◽  
Çiğdem İçhedef ◽  
Kadriye Buşra Karatay ◽  
Serap Teksöz

Backgorund: Superparamagnetic iron oxide nanoparticles (SPIONs) have been extensively used for targeted drug delivery systems due to their unique magnetic properties. Objective: In this study, it’s aimed to develop a novel targeted 99mTc radiolabeled polymeric drug delivery system for Gemcitabine (GEM). Methods: Gemcitabine, an anticancer agent, was encapsulated into polymer nanoparticles (PLGA) together with iron oxide nanoparticles via double emulsion technique and then labeled with 99mTc. SPIONs were synthesized by reduction–coprecipitation method and encapsulated with oleic acid for surface modification. Size distribution and the morphology of the synthesized nanoparticles were caharacterized by dynamic light scattering(DLS)and scanning electron microscopy(SEM), respectively. Radiolabeling yield of SPION-PLGAGEM nanoparticles were determined via Thin Layer Radio Chromatography (TLRC). Cytotoxicity of GEM loaded SPION-PLGA were investigated on MDA-MB-231 and MCF7 breast cancer cells in vitro. Results: SEM images displayed that the average size of the drug-free nanoparticles was 40 nm and the size of the drug-loaded nanoparticles was 50 nm. The diameter of nanoparticles were determined as 366.6 nm by DLS, while zeta potential was found as-29 mV. SPION was successfully coated with PLGA, which was confirmed by FTIR. GEM encapsulation efficiency of SPION-PLGA was calculated as 4±0.16 % by means of HPLC. Radiolabeling yield of SPION-PLGA-GEM nanoparticles were determined as 97.8±1.75 % via TLRC. Cytotoxicity of GEM loaded SPION-PLGA were investigated on MDA-MB-231 and MCF7 breast cancer cells. SPION-PLGA-GEM showed high uptake on MCF-7, whilst incorporation rate was increased for both cell lines which external magnetic field application. Conclusion: 99mTc labeled SPION-PLGA nanoparticles loaded with GEM may overcome some of the obstacles in anti-cancer drug delivery because of their appropriate size, non-toxic, and supermagnetic characteristics.


2020 ◽  
Vol 16 (34) ◽  
pp. 2863-2878
Author(s):  
Yang Liu ◽  
Qian Du ◽  
Dan Sun ◽  
Ruiying Han ◽  
Mengmeng Teng ◽  
...  

Breast cancer is one of the leading causes of cancer-related deaths in women worldwide. Unfortunately, treatments often fail because of the development of drug resistance, the underlying mechanisms of which remain unclear. Circulating tumor DNA (ctDNA) is free DNA released into the blood by necrosis, apoptosis or direct secretion by tumor cells. In contrast to repeated, highly invasive tumor biopsies, ctDNA reflects all molecular alterations of tumors dynamically and captures both spatial and temporal tumor heterogeneity. Highly sensitive technologies, including personalized digital PCR and deep sequencing, make it possible to monitor response to therapies, predict drug resistance and tailor treatment regimens by identifying the genomic alteration profile of ctDNA, thereby achieving precision medicine. This review focuses on the current status of ctDNA biology, the technologies used to detect ctDNA and the potential clinical applications of identifying drug resistance mechanisms by detecting tumor-specific genomic alterations in breast cancer.


Author(s):  
Peng Xie ◽  
Yushu Wang ◽  
Dengshuai Wei ◽  
Lingpu Zhang ◽  
Bin Zhang ◽  
...  

The mechanisms of chemoresistance and nanoparticle-based drug delivery systems for platinum drugs were detailed summarized in this review. The current combination therapy provided an effective strategy to overcome the platinum drug resistance.


2014 ◽  
Vol 43 ◽  
pp. 614-621 ◽  
Author(s):  
Jingyun Wang ◽  
Shuang Cui ◽  
Yongming Bao ◽  
Jishuang Xing ◽  
Wenbo Hao

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