Self‐Assembly of Cell–Microparticle Hybrids

Krishnamachari, Yogita; Pearce, Megan; Salem, Aliasger K.

doi:10.1002/adma.200701689

Cited by 36 publications

(33 citation statements)

References 30 publications

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“…coiled-coil peptide/protein recognition, antibody-antigen binding and DNA hybridization. The high-fidelity self-assembling nature motifs and their mimics can be employed to label/functionalize cell surfaces [1], influence immune response [2], control cell signaling pathways [3–5], manipulate cell fate [6–7], and trigger cellular events [3,8–17]. Biorecognition forms the basis for the design of precisely defined smart systems, including targeted therapeutics [10,12], imaging agents, stimuli-sensitive and self-assembled biomaterials [18], and biosensors [19].…”

Section: Introductionmentioning

confidence: 99%

Drug-free macromolecular therapeutics: Impact of structure on induction of apoptosis in Raji B cells

Zhang

Fang

Yang

et al. 2017

Journal of Controlled Release

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Recently, we developed a new paradigm in macromolecular therapeutics that avoids the use of low molecular weight drugs. The activity of the “drug-free macromolecular therapeutics” is based on the biorecognition of complementary motifs at cell surface resulting in receptor crosslinking and apoptosis induction. The system is composed of two nanoconjugates: (1) a single-stranded morpholino oligonucleotide (MORF1) attached to an anti-CD20 Fab′ fragment (Fab′-MORF1); (2) multiple copies of complementary oligonucleotide MORF2 grafted to a linear polymer of N-(2-hydroxypropyl)methacrylamide (HPMA) – P-(MORF2)x. The two conjugates crosslink CD20 antigens via MORF1-MORF2 hybridization at the surface of CD20+ malignant B-cells and induce apoptosis. Preclinical studies in a murine model of human non-Hodgkin’s lymphoma showed cancer cells eradication and long-term survivors. The aim of this study was to determine the relationship between the detailed structure of the nanoconjugates and apoptosis induction in Raji cells to allow system optimization. The factors studied include the length of the MORF sequence, the valence of P-(MORF2)x (varying x), molecular weight of P-(MORF2)x, incorporation of a miniPEG spacer between Fab′ and MORF1 and between polymer backbone and pendant MORF2, and comparison of two Fab′ fragments, one from 1F5 antibody (Fab′1F5), the other from Rituximab (Fab′RTX). The results of apoptosis induction in human Burkitt’s B-cell non-Hodgkin’s lymphoma (NHL) Raji cells as determined using three apoptotic assays (Annexin V, Caspase 3, and TUNEL) indicated that: a) An improvement of apoptotic activity was observed for a 28 base pair MORF sequence when compared to MORFs composed of 20 and 25 base pairs. The differences depended on type of assay, concentration and exposure schedule (consecutive vs. premixed). b) The higher the valence of P-(MORF2)x the higher the levels of apoptosis. c) Higher molecular weight of P-(MORF2)x induced higher levels of apoptosis. d) A miniPEG8 spacer was effective in enhancing apoptotic levels in contrast to a miniPEG2 spacer. e) There was not a statistically significant difference when comparing Fab′1F5-MORF1 with Fab′RTX-MORF1.

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Section: Introductionmentioning

confidence: 99%

Drug-free macromolecular therapeutics: Impact of structure on induction of apoptosis in Raji B cells

Zhang

Fang

Yang

et al. 2017

Journal of Controlled Release

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“…This was accomplished using an established protocol to introduce exogenous avidin moieties on the cell surface as depicted in Figure 3a. [28] Briefly, cell surface sialic acid moieties were oxidized to generate aldehyde groups that reacted with biotin hydrazide to form a covalent hydrazone bond. The biotinylated NSCs were then coupled to the biotinylated pH-responsive NPs using an avidin linker.…”

Section: Nscs Retain Tumour Tropism In Vitro Following Surface Conjugmentioning

confidence: 99%

“…This design was initially selected based on a manuscript describing its successful use to attach microparticles to cells. [28] The use of the biotin/avidin linking strategy was continued in the current report to allow for rapid evaluation of the potential of our NSC-NP strategy to be used for drug delivery. It is likely that for future translational work an alternative linker strategy will have to be developed to avoid potential immunogenicity concerns.…”

mentioning

confidence: 99%

Conjugation of pH-responsive nanoparticles to neural stem cells improves intratumoral therapy

Mooney

Weng

Garcia

et al. 2014

Journal of Controlled Release

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Intratumoral drug delivery is an inherently appealing approach for concentrating toxic chemotherapies at the site of action. This mode of administration is currently used in a number of clinical treatments such as neoadjuvant, adjuvant, and even standalone therapies when radiation and surgery are not possible. However, even when injected locally, it is difficult to achieve efficient distribution of chemotherapeutics throughout the tumor. This is primarily attributed to the high interstitial pressure which results in gradients that drive fluid away from the tumor center. The stiff extracellular matrix also limits drug penetration throughout the tumor. We have previously shown that neural stem cells can penetrate tumor interstitium, actively migrating even to hypoxic tumor cores. When used to deliver therapeutics, these migratory neural stem cells result in dramatically enhanced tumor coverage relative to conventional delivery approaches. We recently showed that neural stem cells maintain their tumor tropic properties when surface-conjugated to nanoparticles. Here we demonstrate that this hybrid delivery system can be used to improve the efficacy of docetaxel-loaded nanoparticles when administered intratumorally. This was achieved by conjugating drug-loaded nanoparticles to the surface of neural stem cells using a bond that allows the stem cells to efficiently distribute nanoparticles throughout the tumor before releasing the drug for uptake by tumor cells. The modular nature of this system suggests that it could be used to improve the efficacy of many chemotherapy drugs after intratumoral administration.

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“…Biotinylation of cell surfaces is most frequently used through reaction of primary amine groups on the cell membrane with amine-reactive biotin, such as N-hydroxy-succinimide biotin derivatives (NHS-biotin). Once a cell is labeled with biotin, it can be readily functionalized with a wide range of biotinylated molecules through the biotin-avidin interaction [60,61] (Figure 3B). Sakai et al [62] applied a rapid cell-cell adhesion method for construction of heterospheroids with homogenous distribution of different cell types, using NHS-biotin derivatives through the biotin-avidin interaction.…”

Section: Chemical Cell Surface Modificationmentioning

confidence: 99%