Effect of redox‐responsive DTSSP crosslinking on poly(l‐lysine)‐grafted‐poly(ethylene glycol) nanoparticles for delivery of proteins

Abstract

Therapeutic proteins are utilized in a variety of clinical applications, but side effects and rapid in vivo clearance still present hurdles. An approach that addresses both drawbacks is protein encapsulation within in a polymeric nanoparticle, which is effective but introduces the additional challenge of destabilizing the nanoparticle shell in clinically-relevant locations. This study examined the effects of crosslinking self-This is the author manuscript accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as

Hybrid Nanosystems for Biomedical Applications

“…Some polymers such as polydopamine (PDA) convert incident light into thermal energy, allowing them to be used as LSPR-independent photoabsorbers . Regularly, two or more polymers are combined into the block or grafted copolymers like poly­(lactic- co -glycolic acid) (PLGA) to combine the functionalities of constituent polymers and introduce previously unrealized functionality …”

“…The tumor microenvironment of several cancers has been reported to disproportionately express folate receptors, CD44 receptors, and α V β 3 integrins, which can be actively targeted by folic acid (FA), hyaluronic acid (HA), and arginine-glycine-aspartic (RGD) peptides, respectively. ,, Cyclic targeting ligand iRGD utilizes a two-step process to sequentially target α V integrins and neuropilin-1 via a CendR interaction following proteolytic cleavage . Finally, nanosystems can be modified with redox/pH-sensitive moieties, cross-linked to control therapeutic loading and release profiles, or functionalized to alter nucleic acid condensation. , Reviews on active targeting in biomedical nanosystems can be obtained from Muhamad, Plengsuriyakarn, and Na-Banchang and Bazak et al Targeting ligands and antibodies have been included in hybrid nanosystems throughout the biomedical field. Figure describes the organic and accessory building blocks for hybrid nanosystems.…”

“…141 Regularly, two or more polymers are combined into the block or grafted copolymers like poly-(lactic-co-glycolic acid) (PLGA) to combine the functionalities of constituent polymers and introduce previously unrealized functionality. 142 The method of polymer synthesis for a hybrid nanosystem is both material and system dependent. For example, the natural polymer chitosan is isolated from the shells of crustaceans, 143 whereas synthetic polymers such as PEI are formed through addition or condensation reactions.…”

“…189 Finally, nanosystems can be modified with redox/pH-sensitive moieties, cross-linked to control therapeutic loading and release profiles, or functionalized to alter nucleic acid condensation. 142,190 Reviews on active targeting in biomedical nanosystems can be obtained from Muhamad, Plengsuriyakarn, and Na-Banchang 191 and Bazak et al 192 Targeting ligands and antibodies have been included in hybrid nanosystems throughout the biomedical field. Figure 5 describes the organic and accessory building blocks for hybrid nanosystems.…”

Advanced Delivery Systems Based on Lysine or Lysine Polymers

“…Seaberg et al synthesized selfassembled poly-L-lysine-grafted-polyethylene glycol NPs with redox-responsive 3,3′-dithiobis(sulfosuccinimidyl propionate) (DTSSP) for the delivery of protein. 142 Containing a glutathione-reducible disulfide, DTSSP is reduced in the presence of glutathione, which is present in high concentrations in cancer cells. As a result of this reduction, NPs are destabilized and release the encapsulated protein.…”