Self-immolative polyplexes for DNA delivery

Sirianni, Quinton E. A.; Wang, Tian Duo; Borecki, Aneta; Deng, Zhicheng; Ronald, John A.; Gillies, Elizabeth R.

doi:10.1039/d1bm01684a

Cited by 10 publications

(11 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…331,332 These nanoparticles showed potential for successful nucleic delivery, which is possibly enhanced by the ability to release cargo as a result of the polymer depolymerization. 333 Poly(disulfides) are redox-responsive polymers that can undergo rapid and complete self-immolation in biological reducing environments such as the cytosol, which contains significant levels of GSH, an endogenous reducing agent. Poly(lipoic acid) (PLp) and its derivatives can depolymerize (self-immolate) via its backbone, where thiol-induced chain scission takes place (Figure 23C).…”

Section: Stimuli-responsive Polymersmentioning

confidence: 99%

“…Another method to reduce toxicity is to utilize biodegradable functionality. Sirianni et al designed a PIC that was based on self-immolative PGAm rather than PEI, and was able to undergo endogenous pH-responsive depolymerization . This biodegradable PIC encapsulated plasmid DNA and provided similar gene expression levels to PEI functionalized PICs, but was notably less toxic.…”

Section: Spherical Nanoparticlesmentioning

confidence: 99%

“…330 The introduction of certain end-caps can also introduce stimuliresponsive self-immolation to PGAms; some of the stimuli include pH, temperature, and redox environment. 331,332 These nanoparticles showed potential for successful nucleic delivery, which is possibly enhanced by the ability to release cargo as a result of the polymer depolymerization. 333 Poly(disulfides) are redox-responsive polymers that can undergo rapid and complete self-immolation in biological reducing environments such as the cytosol, which contains significant levels of GSH, an endogenous reducing agent.…”

Section: Stimuli-responsive Polymersmentioning

confidence: 99%

“…Sirianni et al designed a PIC that was based on self-immolative PGAm rather than PEI, and was able to undergo endogenous pH-responsive depolymerization. 332 This biodegradable PIC encapsulated plasmid DNA and provided similar gene expression levels to PEI functionalized PICs, but was notably less toxic. Oupickýet al reported a PIC consisting of anionic RNA and a cationic anti-cancer prodrug, which was functionalized with disulfide moieties.…”

Section: Polyion Complexmentioning

confidence: 99%

See 3 more Smart Citations

Polymeric Nanoparticles for Drug Delivery

Beach,

Nayanathara,

Gao

et al. 2024

Chem. Rev.

View full text Add to dashboard Cite

The recent emergence of nanomedicine has revolutionized the therapeutic landscape and necessitated the creation of more sophisticated drug delivery systems. Polymeric nanoparticles sit at the forefront of numerous promising drug delivery designs, due to their unmatched control over physiochemical properties such as size, shape, architecture, charge, and surface functionality. Furthermore, polymeric nanoparticles have the ability to navigate various biological barriers to precisely target specific sites within the body, encapsulate a diverse range of therapeutic cargo and efficiently release this cargo in response to internal and external stimuli. However, despite these remarkable advantages, the presence of polymeric nanoparticles in wider clinical application is minimal. This review will provide a comprehensive understanding of polymeric nanoparticles as drug delivery vehicles. The biological barriers affecting drug delivery will be outlined first, followed by a comprehensive description of the various nanoparticle designs and preparation methods, beginning with the polymers on which they are based. The review will meticulously explore the current performance of polymeric nanoparticles against a myriad of diseases including cancer, viral and bacterial infections, before finally evaluating the advantages and crucial challenges that will determine their wider clinical potential in the decades to come.

show abstract

Section: Stimuli-responsive Polymersmentioning

confidence: 99%

Section: Spherical Nanoparticlesmentioning

confidence: 99%

Section: Stimuli-responsive Polymersmentioning

confidence: 99%

Section: Polyion Complexmentioning

confidence: 99%

See 2 more Smart Citations

Polymeric Nanoparticles for Drug Delivery

Beach,

Nayanathara,

Gao

et al. 2024

Chem. Rev.

View full text Add to dashboard Cite

show abstract

“…However, these polymers randomly degrade to generate numerous uncontrolled reaction products, and inevitably, additional stimuli are consistently required during multiplicative cleavage reactions. On the other hand, self-immolative polymers that are capable of spontaneous depolymerization are valuable in the design of polymer amphiphiles. − Once triggered, these amphiphiles continuously depolymerize without the need for additional stimuli, and amphiphiles such as poly(benzyl carbamate) and polyglyoxylate are of particular interest. − However, these macromolecules have been merely employed to induce partial disintegration of micellar structures and are still rare, given the potential of self-immolative polymer candidates. Furthermore, the depolymerization-induced disassembly mechanisms have been limitedly explored so far, despite their ability to provide autonomous molecular control of nanoassemblies. ,,, …”

Section: Introductionmentioning

confidence: 99%

Self-Immolative and Amphiphilic Poly(benzyl ether)-Based Copolymers: Synthesis and Triggered Demicellization via Head-to-Tail Depolymerization

Kim

Park

et al. 2022

Macromolecules

View full text Add to dashboard Cite

This paper describes the design of poly(benzyl ether)-based amphiphiles that are capable of selective and molecular demicellization via headto-tail depolymerization, triggered by a specific stimulus. The amphiphiles were synthesized by living anionic polymerization with sequential additions of two quinone methide monomers, followed by postpolymerization reaction. The amphiphiles also effectively formed polymeric micelles under aqueous conditions. The cooperative depolymerization behavior and assembly propensity of the copolymers enabled depolymerization-induced demicellization, which proceeded completely or partially under the control of an applied molecular signal. As a proof of concept, a hydrophobic model drug, doxorubicin, was loaded inside the micelles, which were then degraded on the molecular level, leading to controlled yet complete release of the cargo molecules. It is envisioned that the design concept for the micelles can be further expanded to targeted delivery systems or removable micellar encapsulants.

show abstract

Acid‐Responsive Polymer Additives Increase RNA Transfection from Lipid Nanoparticles

Cheung,

Fuchs,

Shoichet

2024

Adv Funct Materials

View full text Add to dashboard Cite

Lipid nanoparticles (LNPs) are the most clinically advanced RNA delivery technology, but their efficiency is limited by low RNA release after endosome disruption. To improve RNA release, an acid‐responsive polymer is synthesized with which to formulate LNPs for RNA encapsulation and release. Specifically, three acid‐responsive poly(lactic acid)‐block‐poly(carboxybetaine) zwitterionic derivatives are designed and synthesized that are cationic and complexed with RNA at pH 7.4, but are neutral following cleavage at endosomal pH, thereby having lower affinity to RNA. The polymers are formulated into each of the clinically approved Onpattro, Moderna, or Pfizer LNP formulations to produce hybrid polymer‐lipid nanoparticles (PLNPs). With the PLNPs, the IC50 values of multiple small interfering RNAs (siRNAs) decreased up to 5.4‐fold compared to parent LNPs in several cell lines. Moreover, messenger RNA (mRNA) transfection increased up to two fold. The acid‐responsive polymers in PLNPs accounted for the enhanced RNA transfection as this phenomenon is lost with acid‐inert polymers. Confocal microscopy confirmed that cytosolic RNA concentration increased using the acid‐responsive polymers; conversely, uptake and endosomal escape are identical to existing LNPs. This confirmed that enhanced RNA transfection is due to increased RNA dissociation from its carrier. The novel polymer represents a versatile strategy to increase RNA transfection from LNPs.

show abstract

Self-immolative polyplexes for DNA delivery

Abstract: Nucleic acids have immense potential for the treatment and prevention of a wide range of diseases, but delivery vehicles are needed to assist with their entry into cells. Polycations can...

Cited by 10 publications

References 40 publications

Polymeric Nanoparticles for Drug Delivery

Polymeric Nanoparticles for Drug Delivery

Self-Immolative and Amphiphilic Poly(benzyl ether)-Based Copolymers: Synthesis and Triggered Demicellization via Head-to-Tail Depolymerization

Acid‐Responsive Polymer Additives Increase RNA Transfection from Lipid Nanoparticles

Contact Info

Product

Resources

About