Hyaluronic Acid-Functionalized Gold Nanorods with pH/NIR Dual-Responsive Drug Release for Synergetic Targeted Photothermal Chemotherapy of Breast Cancer

Novel reduction-responsive hyaluronic acid–chitosan–lipoic acid nanoparticles (HACSLA-NPs) were designed and synthesized for effective treatment of breast cancer by targeting Cluster of Differentiation 44 (CD44)-overexpressing cells and reduction-triggered 17α-Methyltestosterone (MT) release for systemic delivery. The effectiveness of these nanoparticles was investigated by different assays, including release rate, 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT), lactate dehydrogenase (LDH), caspase-3 activity, Rhodamine 123 (RH-123), and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). In vitro experiments revealed that Methyltestosterone/Hyaluronic acid–chitosan–lipoic acid nanoparticles (MT/HACSLA-NPs) illustrated a sustained drug release in the absence of glutathione (GSH), while the presence of GSH led to fast MT release. HACSLA-NPs also showed high cellular internalization via CD44 receptors, quick drug release inside the cells, and amended cytotoxicity against positive CD44 BT-20 breast cancer cell line as opposed to negative CD44, Michigan Cancer Foundation-7 (MCF-7) cell line. These findings supported that these novel reduction-responsive NPs can be promising candidates for efficient targeted delivery of therapeutics in cancer therapy.

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Novel CD44-targeting and pH/redox-dual-stimuli-responsive core–shell nanoparticles loading triptolide combats breast cancer growth and lung metastasis

Journal of Nanobiotechnology ◽

10.1186/s12951-021-00934-0 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Jinfeng Shi ◽

Yali Ren ◽

Jiaqi Ma ◽

Xi Luo ◽

Jiaxin Li ◽

...

Keyword(s):

Breast Cancer ◽

Hyaluronic Acid ◽

Drug Release ◽

Lung Metastasis ◽

Drug Loading ◽

Tumor Therapy ◽

Systemic Toxicity ◽

Migration And Invasion ◽

Stimuli Responsive ◽

Cd44 Targeting

Abstract Background The toxicity and inefficient delivery of triptolide (TPL) in tumor therapy have greatly limited the clinical application. Thus, we fabricated a CD44-targeting and tumor microenvironment pH/redox-sensitive nanosystem composed of hyaluronic acid-vitamin E succinate and poly (β-amino esters) (PBAEss) polymers to enhance the TPL-mediated suppression of breast cancer proliferation and lung metastasis. Results The generated TPL nanoparticles (NPs) had high drug loading efficiency (94.93% ± 2.1%) and a desirable average size (191 nm). Mediated by the PBAEss core, TPL/NPs displayed a pH/redox-dual-stimuli-responsive drug release profile in vitro. Based on the hyaluronic acid coating, TPL/NPs exhibited selective tumor cellular uptake and high tumor tissue accumulation capacity by targeting CD44. Consequently, TPL/NPs induced higher suppression of cell proliferation, blockage of proapoptotic and cell cycle activities, and strong inhibition of cell migration and invasion than that induced by free TPL in MCF-7 and MDA-MB-231 cells. Importantly, TPL/NPs also showed higher efficacy in shrinking tumor size and blocking lung metastasis with decreased systemic toxicity in a 4T1 breast cancer mouse model at an equivalent or lower TPL dosage compared with that of free TPL. Histological immunofluorescence and immunohistochemical analyses in tumor and lung tissue revealed that TPL/NPs induced a high level of apoptosis and suppressed expression of matrix metalloproteinases, which contributed to inhibiting tumor growth and pulmonary metastasis. Conclusion Collectively, our results demonstrate that TPL/NPs, which combine tumor active targeting and pH/redox-responsive drug release with proapoptotic and antimobility effects, represent a promising candidate in halting breast cancer progression and metastasis while minimizing systemic toxicity. Graphic Abstract

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Designing and Formulation Optimization of Hyaluronic Acid Conjugated PLGA Nanoparticles of Tamoxifen for Tumor Targeting

Pharmaceutical Nanotechnology ◽

10.2174/2211738509666210310155807 ◽

2021 ◽

Vol 09 ◽

Author(s):

Suresh Kumar Paswan ◽

T. R. Saini ◽

Sarwar Jahan ◽

N. Ganesh

Keyword(s):

Breast Cancer ◽

Hyaluronic Acid ◽

Side Effects ◽

Drug Release ◽

Cell Lines ◽

Tumor Targeting ◽

Plga Nanoparticles ◽

Fickian Diffusion ◽

Burst Release ◽

Formulation Optimization

Background: Tamoxifen is widely used for treatment of estrogen receptor positive breast cancer. It is, however, associated with severe side effects of cancerous proliferation on uterus endometrium. The tumor targeting formulation strategies can effectively overcome drug side effects of tamoxifen and provide safer drug treatment. Objective: Designing tumor targeted PLGA nanoparticles of tamoxifen by attaching hyaluronic acid (HA) as ligand to actively target the CD44 receptors present at breast cancer cells surface. Methods: PLGA-PEG-HA conjugate was synthesized in the laboratory and its tamoxifen loaded nanoparticles were fabricated and characterized by FTIR, NMR, DSC, and XRD analysis. Formulation optimization was done by Box- Behnken design using Design Expert software. The formulations were evaluated for in- vitro drug release and cytotoxic effect on MCF-7 cell lines. Results: The particle size, PDI, and drug encapsulation efficiency of optimized nanoparticles were 294.8, 0.626, and 65.16% respectively. Optimized formulation showed 9.56 % burst release and sustained drug release for 8 h. The drug release was effected by non-fickian diffusion process supplemented further by erosion of polymeric matrix and followed korsmeyer-Peppas model. MTT cell line assay shows 47.48 % cell mortality when treated with tamoxifen loaded PLGA-PEG-HA nanoparticles. Conclusion: Hyaluronic acid conjugated PLGA-PEG nanoparticles of tamoxifen were designed for active targeting to breast cancerous cells. The results of MTT assay showed that tamoxifen nanoparticles formulation was more cytotoxic than tamoxifen drug alone which is attributed to their preferential uptake by cell lines by affinity of CD44 receptors of cell lines to HA ligand present in nanoparticles.

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Biocompatible hyaluronic acid-divinyl sulfone injectable hydrogels for sustained drug release with enhanced antibacterial properties against Staphylococcus aureus

Materials Science and Engineering C ◽

10.1016/j.msec.2021.112102 ◽

2021 ◽

pp. 112102

Author(s):

Jon Andrade del Olmo ◽

José María Alonso ◽

Virginia Sáez Martínez ◽

Leire Ruiz-Rubio ◽

Raúl Pérez González ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Hyaluronic Acid ◽

Drug Release ◽

Antibacterial Properties ◽

Sustained Drug Release ◽

Injectable Hydrogels ◽

Divinyl Sulfone

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NIR responsive AuNRs/pNIPAM/PEGDA inverse opal hydrogel microcarriers for controllable drug delivery

New Journal of Chemistry ◽

10.1039/d0nj06289h ◽

2021 ◽

Author(s):

Lingzi Liu ◽

Xiaoyan Sun ◽

Baofen Ye ◽

Zhengyu Yan

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Delivery System ◽

Gold Nanorods ◽

Controlled Drug Release ◽

Inverse Opal

Particle-based delivery system has merged as a powerful platform in controlled drug release. The present study developed a new inverse opal hydrogel microcarriers system composed of gold nanorods (AuNRs) for...

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