Engineering peptide-targeted liposomal nanoparticles optimized for improved selectivity for HER2-positive breast cancer cells to achieve enhanced in vivo efficacy

Kim, Baksun; Shin, Jae-Ho; Wu, Junmin; Omstead, David T.; Kiziltepe, Tanyel; Littlepage, Laurie E.; Bilgiçer, Başar

doi:10.1016/j.jconrel.2020.04.010

Cited by 52 publications

(53 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent advances in CRISPR-based gene editing [220] and the orthotopic transplantation of spontaneous tumors into recipient mice have permitted improvements that have accelerated model development and improved homogeneity of metastatic spread. For example, Kim et al employed MMTV-neu mouse-derived tumors for the in vivo evaluation of peptide-targeted liposomal doxorubicin nanoparticles with enhanced selectivity for HER2-positive breast tumor cells [221] . The authors cryopreserved portions of any spontaneously-arising tumors and then orthotopically transplanted them into female NOD-SCID mice.…”

Section: Pre-clinical Breast Cancer Animal Modelsmentioning

confidence: 99%

The past, present, and future of breast cancer models for nanomedicine development

Boix-Montesinos

Soriano-Teruel

Armiñán

et al. 2021

Advanced Drug Delivery Reviews

View full text Add to dashboard Cite

show abstract

Section: Pre-clinical Breast Cancer Animal Modelsmentioning

confidence: 99%

The past, present, and future of breast cancer models for nanomedicine development

Boix-Montesinos

Soriano-Teruel

Armiñán

et al. 2021

Advanced Drug Delivery Reviews

View full text Add to dashboard Cite

show abstract

“…Cancers that overexpress a specific receptor that simultaneously exists on healthy cells make an ideal target for similar strategies, such as CD20 for B-cell lymphoma or CD30 for Hodgkin’s lymphoma. Our laboratory has also recently developed nanoparticles for selective uptake of CD22 overexpressing B-cell malignancies and HER2 overexpressing breast cancer, proving both to be other possible targets for liposomes designed through the same platform [ 52 , 53 ]. Further preclinical evaluation is needed, such as dosing studies on how much can be given without causing systemic toxicity, and if tumor remission can be achieved with a significantly high dose.…”

Section: Discussionmentioning

confidence: 99%

In vivo evaluation of CD38 and CD138 as targets for nanoparticle-based drug delivery in multiple myeloma

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background Drug-loaded nanoparticles have established their benefits in the fight against multiple myeloma; however, ligand-targeted nanomedicine has yet to successfully translate to the clinic due to insufficient efficacies reported in preclinical studies. Methods In this study, liposomal nanoparticles targeting multiple myeloma via CD38 or CD138 receptors are prepared from pre-synthesized, purified constituents to ensure increased consistency over standard synthetic methods. These nanoparticles are then tested both in vitro for uptake to cancer cells and in vivo for accumulation at the tumor site and uptake to tumor cells. Finally, drug-loaded nanoparticles are tested for long-term efficacy in a month-long in vivo study by tracking tumor size and mouse health. Results The targeted nanoparticles are first optimized in vitro and show increased uptake and cytotoxicity over nontargeted nanoparticles, with CD138-targeting showing superior enhancement over CD38-targeted nanoparticles. However, biodistribution and tumor suppression studies established CD38-targeted nanoparticles to have significantly increased in vivo tumor accumulation, tumor cell uptake, and tumor suppression over both nontargeted and CD138-targeted nanoparticles due to the latter’s poor selectivity. Conclusion These results both highlight a promising cancer treatment option in CD38-targeted nanoparticles and emphasize that targeting success in vitro does not necessarily translate to success in vivo.

show abstract

“…In another study, the importance of composition and density of the tumor-targeting peptide for delivery of the NP-drug complex was explored in HER2-positive breast cancer [115]. The composition of targeting peptide moiety was tuned to investigate the effects in binding avidity as some researchers earlier reported notable effects of composition and density of targeting peptides on receptor affinity and cellular uptake [116][117][118].…”

Section: Her-2 Targeted Drug-loaded Npsmentioning

confidence: 99%

“…TNP HER2PEP [EG 8 ] with a density of 0.25-0.5% showed higher accumulation in the tumor region without any off-target distribution in major organs. DOX-loaded TNP HER2PEP [EG 8 ] with a peptide density of 0.25-0.5% caused 68% reduction in the tumor volume compared to the untargeted formulation in an orthotopic MMTV(Mouse mammary tumor virus)-neu transplantation mouse model without changing the bodyweight of treated mice [115].…”

Section: Her-2 Targeted Drug-loaded Npsmentioning

confidence: 99%

Nanoparticles Targeting Receptors on Breast Cancer for Efficient Delivery of Chemotherapeutics

2021

View full text Add to dashboard Cite

The journey of chemotherapeutic drugs from the site of administration to the site of action is confronted by several factors including low bioavailability, uneven distribution in major organs, limited accessibility of drug molecules to the distant tumor tissues, and lower therapeutic indexes. These unavoidable features of classical chemotherapeutics necessitate an additional high, repetitive dose of drugs to obtain maximum therapeutic responses with the result of unintended adverse side effects. An erratic tumor microenvironment, notable drawbacks of conventional chemotherapy, and multidrug-resistant mechanisms of breast cancer cells warrant precisely designed therapeutics for the treatment of cancers. In recent decades, nanoparticles have been deployed for the delivery of standard anticancer drugs to maximize the therapeutic potency while minimizing the adverse effects to increase the quality and span of life. Several organic and inorganic nanoplatforms that have been designed exploiting the distinctive features of the tumor microenvironment and tumor cells offer favorable physicochemical properties and pharmacokinetic profiles of a parent drug, with delivery of higher amounts of the drug to the pathological site and its controlled release, thereby improving the balance between its efficacy and toxicity. Advances to this front have included design and construction of targeted nanoparticles by conjugating homing devices like peptide, ligand, and Fab on the surface of nanomaterials to navigate nanoparticledrug complexes towards the target tumor cell with minimal destruction of healthy cells. Furthermore, actively targeting nanoparticles can facilitate the delivery and cellular uptake of nanoparticle-loaded drug constructs via binding with specific receptors expressed aberrantly on the surface of a tumor cell. Herein, we present an overview of the principle of targeted delivery approaches, exploiting drug-nanoparticle conjugates with multiple targeting moieties to target specific receptors of breast cancer cells and highlighting therapeutic evaluation in preclinical studies. We conclude that an understanding of the translational gap and challenges would show the possible future directions to foster the development of novel targeted nanotherapeutics.

show abstract

Engineering peptide-targeted liposomal nanoparticles optimized for improved selectivity for HER2-positive breast cancer cells to achieve enhanced in vivo efficacy

Cited by 52 publications

References 41 publications

The past, present, and future of breast cancer models for nanomedicine development

The past, present, and future of breast cancer models for nanomedicine development

In vivo evaluation of CD38 and CD138 as targets for nanoparticle-based drug delivery in multiple myeloma

Nanoparticles Targeting Receptors on Breast Cancer for Efficient Delivery of Chemotherapeutics

Contact Info

Product

Resources

About