Active-targeting and acid-sensitive pluronic prodrug micelles for efficiently overcoming MDR in breast cancer

2020 ◽  
Vol 8 (13) ◽  
pp. 2726-2737
Author(s):  
Cheng Xu ◽  
Jiaxi Xu ◽  
Yan Zheng ◽  
Qin Fang ◽  
Xiaodong Lv ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Self Assembly ◽  
Active Targeting

The mechanism of pluronic-based prodrug micelles self-assembly, drug delivery and anti-MDR in vivo.

scholarly journals Controllable Drug Delivery by Na+/K+ ATPase α1 Targeting Peptide Conjugated DSPE-PEG Nanocarriers for Breast Cancer

2021 ◽  
Vol 20 ◽  
pp. 153303382110278
Author(s):  
Yayan Yang ◽  
Qian Feng ◽  
Chuanfeng Ding ◽  
Wei Kang ◽  
Xiufeng Xiao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Click Reaction ◽  
Chemotherapy Drugs ◽  
Targeting Peptide ◽  
And Migration

Although Epirubicin (EPI) is a commonly used anthracycline for the treatment of breast cancer in clinic, the serious side effects limit its long-term administration including myelosuppression and cardiomyopathy. Nanomedicines have been widely utilized as drug delivery vehicles to achieve precise targeting of breast cancer cells. Herein, we prepared a DSPE-PEG nanocarrier conjugated a peptide, which targeted the breast cancer overexpression protein Na+/K+ ATPase α1 (NKA-α1). The nanocarrier encapsulated the EPI and grafted with the NKA-α1 targeting peptide through the click reaction between maleimide and thiol groups. The EPI was slowly released from the nanocarrier after entering the breast cancer cells with the guidance of the targeting NKA-α1 peptide. The precise and controllable delivery and release of the EPI into the breast cancer cells dramatically inhibited the cells proliferation and migration in vitro and suppressed the tumor volume in vivo. These results demonstrate significant prospects for this nanocarrier as a promising platform for numerous chemotherapy drugs.

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 ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Drug Resistance ◽  
Cancer Therapy ◽  
Self Assembly ◽  
Cancer Drug ◽  
Acquired Drug Resistance ◽  
Self Assembling ◽  
Amphiphilic Peptide ◽  
Peptide Dendrimer

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.

Efficacy of a novel LyP-1-containing self-microemulsifying drug delivery system (SMEDDS) for active targeting to breast cancer

2019 ◽  
Vol 136 ◽  
pp. 138-146 ◽  
Author(s):  
Selin S. Timur ◽  
Diğdem Yöyen-Ermiş ◽  
Güldal Esendağlı ◽  
Selcen Yonat ◽  
Utku Horzum ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Active Targeting

scholarly journals The Therapeutic Efficacy of Dendrimer and Micelle Formulations for Breast Cancer Treatment

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1212
Author(s):  
Sibusiso Alven ◽  
Blessing Atim Aderibigbe
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Drug Resistance ◽  
Side Effects ◽  
Anticancer Drugs ◽  
Drug Toxicity ◽  
Multi Drug Resistance ◽  
Drug Bioavailability

Breast cancer is among the most common types of cancer in women and it is the cause of a high rate of mortality globally. The use of anticancer drugs is the standard treatment approach used for this type of cancer. However, most of these drugs are limited by multi-drug resistance, drug toxicity, poor drug bioavailability, low water solubility, poor pharmacokinetics, etc. To overcome multi-drug resistance, combinations of two or more anticancer drugs are used. However, the combination of two or more anticancer drugs produce toxic side effects. Micelles and dendrimers are promising drug delivery systems that can overcome the limitations associated with the currently used anticancer drugs. They have the capability to overcome drug resistance, reduce drug toxicity, improve the drug solubility and bioavailability. Different classes of anticancer drugs have been loaded into micelles and dendrimers, resulting in targeted drug delivery, sustained drug release mechanism, increased cellular uptake, reduced toxic side effects of the loaded drugs with enhanced anticancer activity in vitro and in vivo. This review article reports the biological outcomes of dendrimers and micelles loaded with different known anticancer agents on breast cancer in vitro and in vivo.

CD44 targeted redox-triggered self-assembly with magnetic enhanced EPR effects for effective amplification of gambogic acid to treat triple-negative breast cancer

2020 ◽  
Vol 8 (1) ◽  
pp. 212-223 ◽  
Author(s):  
Mangmang Sang ◽  
Lingfei Han ◽  
Renjie Luo ◽  
Wei Qu ◽  
Feng Zheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Self Assembly ◽  
Triple Negative ◽  
Gambogic Acid

Scheme of mPEG-HA/CSO-SS-Hex/SPION/GA self-assembly preparation and the magnetism-enhanced EPR in vivo and in vitro trafficking pathways of the polymeric self-assembly.

scholarly journals Peptide Nanomaterials for Drug Delivery Applications

2020 ◽  
Vol 21 (4) ◽  
pp. 401-412 ◽  
Author(s):  
Sreekanth Pentlavalli ◽  
Sophie Coulter ◽  
Garry Laverty
Keyword(s):  
Drug Delivery ◽  
Self Assembly ◽  
Diverse Range ◽  
Drug Molecules ◽  
Sustained Drug Delivery ◽  
Self Assembling ◽  
Wide Range ◽  
Methods Of Synthesis ◽  
Self Assembled

Self-assembled peptides have been shown to form well-defined nanostructures which display outstanding characteristics for many biomedical applications and especially in controlled drug delivery. Such biomaterials are becoming increasingly popular due to routine, standardized methods of synthesis, high biocompatibility, biodegradability and ease of upscale. Moreover, one can modify the structure at the molecular level to form various nanostructures with a wide range of applications in the field of medicine. Through environmental modifications such as changes in pH and ionic strength and the introduction of enzymes or light, it is possible to trigger self-assembly and design a host of different self-assembled nanostructures. The resulting nanostructures include nanotubes, nanofibers, hydrogels and nanovesicles which all display a diverse range of physico-chemical and mechanical properties. Depending on their design, peptide self-assembling nanostructures can be manufactured with improved biocompatibility and in vivo stability and the ability to encapsulate drugs with the capacity for sustained drug delivery. These molecules can act as carriers for drug molecules to ferry cargo intracellularly and respond to stimuli changes for both hydrophilic and hydrophobic drugs. This review explores the types of self-assembling nanostructures, the effects of external stimuli on and the mechanisms behind the assembly process, and applications for such technology in drug delivery.

scholarly journals Combinatorial nanocarrier based drug delivery approach for amalgamation of anti-tumor agents in breast cancer cells: an improved nanomedicine strategy

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Chandran Murugan ◽  
Kathirvel Rayappan ◽  
Ramar Thangam ◽  
Ramasamy Bhanumathi ◽  
Krishnamurthy Shanthi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Structural Changes ◽  
Silica Nanoparticle ◽  
Therapeutic Effects ◽  
Multiple Drugs

Abstract Combination therapy of multiple drugs through a single system is exhibiting high therapeutic effects. We investigate nanocarrier mediated inhibitory effects of topotecan (TPT) and quercetin (QT) on triple negative breast cancer (TNBC) (MDA-MB-231) and multi drug resistant (MDR) type breast cancer cells (MCF-7) with respect to cellular uptake efficiency and therapeutic mechanisms as in vitro and in vivo. The synthesized mesoporous silica nanoparticle (MSN) pores used for loading TPT; the outer of the nanoparticles was decorated with poly (acrylic acid) (PAA)-Chitosan (CS) as anionic inner-cationic outer layer respectively and conjugated with QT. Subsequently, grafting of arginine-glycine-aspartic acid (cRGD) peptide on the surface of nanocarrier (CPMSN) thwarted the uptake by normal cells, but facilitated their uptake in cancer cells through integrin receptor mediated endocytosis and the dissociation of nanocarriers due to the ability to degrade CS and PAA in acidic pH, which enhance the intracellular release of drugs. Subsequently, the released drugs induce remarkable molecular activation as well as structural changes in tumor cell endoplasmic reticulum, nucleus and mitochondria that can trigger cell death. The valuable CPMSNs may open up new avenues in developing targeted therapeutic strategies to treat cancer through serving as an effective drug delivery podium.

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