Relationships between Poly(ethylene glycol) Modifications on RNA–Spherical Nucleic Acid Conjugates and Cellular Uptake and Circulation Time

Chinen, Alyssa B.; Ferrer, Jennifer R.; Merkel, Timothy J.; Mirkin, Chad A.

doi:10.1021/acs.bioconjchem.6b00483

Cited by 29 publications

(30 citation statements)

References 40 publications

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“…OxPt/DHA are optimally sized pegylated nanoparticles that are large enough to avoid renal filtration (~10 nm) but small enough to penetrate through the leaky tumour vasculatures in tumours 41–43 . The use of ~20 mol% PEG in this formulation helps to reduce plasma protein binding, thus minimizing MPS uptake after systemic injection 44–48 . OxPt/DHA showed low uptake in the liver and other major organs associated with clearance, and significantly increased both the single and repeated dose MTDs of OxPt.…”

Section: Discussionmentioning

confidence: 99%

Immunostimulatory nanomedicines synergize with checkpoint blockade immunotherapy to eradicate colorectal tumors

et al. 2019

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Nanoparticles can potentially stimulate tumour microenvironments to elicit antitumour immunity. Herein, we demonstrate effective immunotherapy of colorectal cancer via systemic delivery of an immunostimulatory chemotherapeutic combination in nanoscale coordination polymer (NCP) core-shell particles. Oxaliplatin and dihydroartemesinin have contrasting physicochemical properties but strong synergy in reactive oxygen species (ROS) generation and anticancer activity. The combined ROS generation is harnessed for immune activation to synergize with an anti-PD-L1 antibody for the treatment of murine colorectal cancer tumours. The favourable biodistribution and tumour uptake of NCPs and the absence of peripheral neuropathy allow for repeated dosing to afford 100% tumour eradication. The involvement of innate and adaptive immune systems elicit strong and long lasting antitumour immunity which prevents tumour formation when cured mice are challenged with cancer cells. The intrinsically biodegradable, well tolerated, and systemically available immunostimulatory NCP promises to enter clinical testing as an immunotherapy against colorectal cancer.

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Section: Discussionmentioning

confidence: 99%

Immunostimulatory nanomedicines synergize with checkpoint blockade immunotherapy to eradicate colorectal tumors

et al. 2019

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“…Although some siRNA delivery applications have been carried out by inorganic SNAs, [138][139][140] there still exist drawbacks, such as the nanoparticle-determined chemical functionalization efficiency and the accumulation-induced cytotoxicity. [141] Gianneschi's group synthesized an RNA-polymer amphiphile, which self-assembled into organic SNAs with about 100 RNA strands on the surface.…”

Section: Instance Of Applicationsmentioning

confidence: 99%

Hydrophobic Interaction: A Promising Driving Force for the Biomedical Applications of Nucleic Acids

et al. 2020

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The comprehensive understanding and proper use of supramolecular interactions have become critical for the development of functional materials, and so is the biomedical application of nucleic acids (NAs). Relatively rare attention has been paid to hydrophobic interaction compared with hydrogen bonding and electrostatic interaction of NAs. However, hydrophobic interaction shows some unique properties, such as high tunability for application interest, minimal effect on NA functionality, and sensitivity to external stimuli. Therefore, the widespread use of hydrophobic interaction has promoted the evolution of NA-based biomaterials in higher-order self-assembly, drug/gene-delivery systems, and stimuli-responsive systems. Herein, the recent progress of NA-based biomaterials whose fabrications or properties are highly determined by hydrophobic interactions is summarized. 1) The hydrophobic interaction of NA itself comes from the accumulation of base-stacking forces, by which the NAs with certain base compositions and chain lengths show properties similar to thermal-responsive polymers. 2) In conjugation with hydrophobic molecules, NA amphiphiles show interesting self-assembly structures with unique properties in many new biosensing and therapeutic strategies. 3) The working-mechanisms of some NA-based complex materials are also dependent on hydrophobic interactions. Moreover, in recent attempts, NA amphiphiles have been applied in organizing macroscopic self-assembly of DNA origami and controlling the cell-cell interactions.

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“…Alternatively, PEGylation of the nanoparticle core has shown the ability to reduce nonspecific adsorption of serum proteins, thus extending blood circulation times, but such modifications compromise SNA uptake efficiency by target cells. 47…”

Section: Introductionmentioning

confidence: 99%

Spherical Nucleic Acids with Tailored and Active Protein Coronae

2019

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Spherical nucleic acids (SNAs) are nanomaterials typically consisting of a nanoparticle core and a functional, dense, and highly oriented oligonucleotide shell with unusual biological properties that make them appealing for many applications, including sequence-specific gene silencing, mRNA quantification, and immunostimulation. When placed in biological fluids, SNAs readily interact with serum proteins, leading to the formation of ill-defined protein coronae on the surface, which can influence the targeting capabilities of the conjugate. In this work, SNAs were designed and synthesized with functional proteins, such as antibodies and serum albumin, deliberately adsorbed onto their surfaces. These particles exhibit increased resistance to protease degradation compared with native SNAs but still remain functional, as they can engage in hybridization with complementary oligonucleotides. SNAs with adsorbed targeting antibodies exhibit improved cellular selectivity within mixed cell populations. Similarly, SNAs coated with the dysopsonizing protein serum albumin show reduced macrophage uptake, providing a strategy for tailoring selective SNA delivery. Importantly, the protein coronae remain stable on the SNAs in human serum, exhibiting a less than 45% loss of protein through exchange after 12 h at 37 °C. Taken together, these results show that protein–SNA complexes and the method used to prepare them provide a new avenue for enhancing SNA stability, targeting, and biodistribution.

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Relationships between Poly(ethylene glycol) Modifications on RNA–Spherical Nucleic Acid Conjugates and Cellular Uptake and Circulation Time

Cited by 29 publications

References 40 publications

Immunostimulatory nanomedicines synergize with checkpoint blockade immunotherapy to eradicate colorectal tumors

Immunostimulatory nanomedicines synergize with checkpoint blockade immunotherapy to eradicate colorectal tumors

Hydrophobic Interaction: A Promising Driving Force for the Biomedical Applications of Nucleic Acids

Spherical Nucleic Acids with Tailored and Active Protein Coronae

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