A library of aminoglycoside-derived lipopolymer nanoparticles for delivery of small molecules and nucleic acids

Sudhakar, Gangarajula; Miryala, Bhavani; Dutta, Subhadeep; Christensen, Matthew D.; Nandi, Purbasha; Chiu, Po-Lin; Rege, Kaushal

doi:10.1039/d0tb00924e

Cited by 4 publications

(2 citation statements)

References 67 publications

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“…[ 151 ] Further, a series of alkanoyl was modified on the PAE polymers to facilitate their self‐assembly, and the resulting nanoparticles demonstrated great promise in the co‐delivery of small‐molecule drugs and plasmid DNA. [ 152 ]…”

Section: Aminoglycoside‐based Biomaterialsmentioning

confidence: 99%

Aminoglycoside‐Based Biomaterials: From Material Design to Antibacterial and Gene Delivery Applications

Yang

Cheng

et al. 2021

Adv Funct Materials

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Aminoglycosides are a family of naturally isolated or chemically semi‐synthesized antibiotics consisting of aminocyclitols with several amino and saccharide units. The unique molecule structures render aminoglycosides promising building blocks with high reactivity to perform various non‐covalent and covalent reactions, and they are further employed to rationally fabricate versatile materials, such as hydrogels, amphiphiles, hyperbranched polymers, biointerfaces, and nanoparticles. Despite aminoglycosides are widely used in clinics to treat bacterial infections, almost all the efforts are focused on molecular modifications to reduce their toxicities and overcome antibiotic resistance, while their actions as building blocks to construct biomaterials are scarcely discussed. In this feature article, the current progress on the rational design, emergent properties, and promising biological applications of aminoglycoside‐based biomaterials are summarized. It is believed that this paper may provide guidance to develop new biomaterials using natural functional molecules as building blocks, and start a new life of aminoglycosides from the view of materials science.

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Section: Aminoglycoside‐based Biomaterialsmentioning

confidence: 99%

Aminoglycoside‐Based Biomaterials: From Material Design to Antibacterial and Gene Delivery Applications

Yang

Cheng

et al. 2021

Adv Funct Materials

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“…Computational chemistry tools, such as density functional theory, are used to calculate molecular descriptors or fingerprint descriptors of the repeat units of the polymers, by breaking each representative chemical block into constituent atomic and molecular fragments. , Thus, any polymer in the chemical space can be parametrized by a series of numbers, which can subsequently be correlated with material properties, such as ζ-potential, p K a , and hydrophobicity, as well as cellular responses, such as nucleic acid binding, cytotoxicity, and transfection efficiency. Using this cheminformatic workflow, Rege and co-workers were able to discover aminoglycoside polymers that mediated high levels of transgene expression. − Algorithms, such as support vector regression and partial least-squares regression quantified the contribution of hydrophobicity, lipid substitution, and molecular weight, allowing them to understand the role of each physicochemical descriptor (Figure A). Despite the molecular understanding and predictive accuracy achieved from forward-QSPR models, inverse-QSPR − or algorithmic design of polymeric vectors was not attempted.…”

Section: Data-driven Design Of Polymeric Vectorsmentioning

confidence: 99%

Materiomically Designed Polymeric Vehicles for Nucleic Acids: Quo Vadis?

Kumar

2022

ACS Appl. Bio Mater.

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Despite rapid advances in molecular biology, particularly in site-specific genome editing technologies, such as CRISPR/Cas9 and base editing, financial and logistical challenges hinder a broad population from accessing and benefiting from gene therapy. To improve the affordability and scalability of gene therapy, we need to deploy chemically defined, economical, and scalable materials, such as synthetic polymers. For polymers to deliver nucleic acids efficaciously to targeted cells, they must optimally combine design attributes, such as architecture, length, composition, spatial distribution of monomers, basicity, hydrophilic−hydrophobic phase balance, or protonation degree. Designing polymeric vectors for specific nucleic acid payloads is a multivariate optimization problem wherein even minuscule deviations from the optimum are poorly tolerated. To explore the multivariate polymer design space rapidly, efficiently, and fruitfully, we must integrate parallelized polymer synthesis, high-throughput biological screening, and statistical modeling. Although materiomics approaches promise to streamline polymeric vector development, several methodological ambiguities must be resolved. For instance, establishing a flexible polymer ontology that accommodates recent synthetic advances, enforcing uniform polymer characterization and data reporting standards, and implementing multiplexed in vitro and in vivo screening studies require considerable planning, coordination, and effort. This contribution will acquaint readers with the challenges associated with materiomics approaches to polymeric gene delivery and offers guidelines for overcoming these challenges. Here, we summarize recent developments in combinatorial polymer synthesis, high-throughput screening of polymeric vectors, omics-based approaches to polymer design, barcoding schemes for pooled in vitro and in vivo screening, and identify materiomics-inspired research directions that will realize the long-unfulfilled clinical potential of polymeric carriers in gene therapy.

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Evaluation of drug carrier hepatotoxicity using primary cell culture models

Kibar¹,

Dutta²,

Rege³

et al. 2023

Nanomedicine: Nanotechnology, Biology and Medicine

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A library of aminoglycoside-derived lipopolymer nanoparticles for delivery of small molecules and nucleic acids

Abstract: Simultaneous delivery of small molecules and nucleic acids using a single vehicle can lead to novel combination treatments and multifunctional carriers for a variety of diseases. In this study, we...

Cited by 4 publications

References 67 publications

Aminoglycoside‐Based Biomaterials: From Material Design to Antibacterial and Gene Delivery Applications

Aminoglycoside‐Based Biomaterials: From Material Design to Antibacterial and Gene Delivery Applications

Materiomically Designed Polymeric Vehicles for Nucleic Acids: Quo Vadis?

Evaluation of drug carrier hepatotoxicity using primary cell culture models

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