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Targeted drug delivery strategies for precision medicines.

ABSTRACT: Progress in the field of precision medicine has changed the landscape of cancer therapy. Precision medicine is propelled by technologies that enable molecular profiling, genomic analysis, and optimized drug design to tailor treatments for individual patients. Although precision medicines have resulted in some clinical successes, the use of many potential therapeutics has been hindered by pharmacological issues, including toxicities and drug resistance. Drug delivery materials and approaches have now advanced to a point where they can enable the modulation of a drug's pharmacological parameters without compromising the desired effect on molecular targets. Specifically, they can modulate a drug's pharmacokinetics, stability, absorption, and exposure to tumours and healthy tissues, and facilitate the administration of synergistic drug combinations. This Review highlights recent progress in precision therapeutics and drug delivery, and identifies opportunities for strategies to improve the therapeutic index of cancer drugs, and consequently, clinical outcomes.

SUBMITTER: Manzari MT

PROVIDER: S-EPMC8691416 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Targeted drug delivery strategies for precision medicines.

Manzari Mandana T MT Shamay Yosi Y Kiguchi Hiroto H Rosen Neal N Scaltriti Maurizio M Heller Daniel A DA

Nature reviews. Materials 20210202 4

Progress in the field of precision medicine has changed the landscape of cancer therapy. Precision medicine is propelled by technologies that enable molecular profiling, genomic analysis, and optimized drug design to tailor treatments for individual patients. Although precision medicines have resulted in some clinical successes, the use of many potential therapeutics has been hindered by pharmacological issues, including toxicities and drug resistance. Drug delivery materials and approaches have ...[more]

PMID: 34950512

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Project description:Drug delivery requires precision in timing, location, and dosage to achieve therapeutic benefits. Challenges in addressing all three of these critical criteria result in poor temporal dexterity, widespread accumulation and off-target effects, and high doses with the potential for toxicity. To address these challenges, we have developed the BiomatErial Accumulating Carriers for On-demand Nanotherapy (BEACON) platform that utilizes an implantable biomaterial to serve as a target for systemically delivered nanoparticles (NPs). With the BEACON system, administered NPs are conjugated with a ligand that has high affinity for a receptor in the implanted biomaterial. To test BEACON, an in vivo spinal cord injury (SCI) model was used as it provides an injury model where the three identified criteria can be tested as it is a dynamic and complicated injury model with no currently approved therapies. Through our work, we have demonstrated temporal dexterity in NP administration by injecting 6 days post-SCI, decreased off-target accumulation with a significant drop in liver accumulation, and retention of our NPs in the target biomaterial. The BEACON system can be applied broadly, beyond the nervous system, to improve systemically delivered NP accumulation at an implanted biomaterial target. STATEMENT OF SIGNIFICANCE: Targeted drug delivery approaches have the potential to improve therapeutic regimens for patients on a case-by-case basis. Improved localization of a therapeutic to site of interest can result in increased efficacy and limit the need for repeat dosing. Unfortunately, targeted strategies can fall short when receptors on cells or tissues are too widespread or change over the course of disease or injury progression. The BEACON system developed herein eliminates the need to target a cell or tissue receptor by targeting an implantable biomaterial with location-controllable accumulation and sustained presentation over time. The targeting paradigm presented by BEACON is widely applicable throughout tissue engineering and regenerative medicine without the need to retool for each new application.

Dataset Information

Targeted drug delivery strategies for precision medicines.

Publications

Targeted drug delivery strategies for precision medicines.

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