In situlow-immunogenic albumin-conjugating-corona guiding nanoparticles for tumor-targeting chemotherapy

Abstract

Nanoparticles (NPs) are unavoidably covered by a layer of immunogenic proteins upon injection into blood, such as immunoglobins and complements, which buries the active-targeting ligands and triggers the rapid clearance of NPs by the mononuclear phagocytic system. Low antifouling polyethylene glycol is used to inhibit the formation of the immunogenic corona but it leads to poor cellular uptake and the immunogen-related accelerated blood clearance (ABC) phenomenon in multiple administrations. Here, we develop surface maleimide-modified NPs that covalently conjugate in vivo plasma albumin in its corona upon exposure to blood. The in situ recruited low-immunogenic albumin-enriching corona is capable of protecting maleimide-decorated NPs from phagocytosis in the bloodstream, preventing the ABC phenomenon in the second administration, facilitating NP accumulation in the tumor site/cells by the passive EPR effect and albumin receptor-mediated active targeting, and finally improving the antitumor activity. Such findings suggest that the facile strategy, based on the in situ anchored albumin-enriching corona, is efficient at enabling maleimide-decorated NPs to acquire stealth and tumor-targeting ability.

Recent Advances in Understanding the Protein Corona of Nanoparticles and in the Formulation of “Stealthy” Nanomaterials

“…Following the idea of some commercially available albuminbased drug delivery systems (e.g., Abraxane), Li et al formulated a novel formulation of PLGA NPs coated with PEG presenting on its surface-reactive maleimide moieties (Li et al, 2018). The rationale of this design is the high reactivity and relative selectivity of maleimide with albumin by covalently binding the cysteine-34 on this protein.…”

In situ apolipoprotein E-enriched corona guides dihydroartemisinin-decorating nanoparticles towards LDLr-mediated tumor-homing chemotherapy

“…Unloaded DTX of PP NPs and PPD NPs was removed by centrifugation at rate of 3500 rpm for 30 min. Then, entrapped DTX was dissolved using acetonitrile and determined by HPLC method [25] . The corresponding DL and EE were calculated as follow: …”

“…Protein corona was isolated from NPs by centrifugation after incubation with rat serum for 1 h [25] , [26] . Taking PPD NPs as an example, incubated PPD NPs were washed by the repeated centrifugation (16 000 g for 10 min) and resuspension process with PBS to isolate weak-adsorbed soft corona.…”

“…To achieve the LDLr-overexpressed 4T1 cells (4T1-G), 4T1 cells were in RPMI-1640 medium supplemented with 2% ultroser G medium, instead of 10% FBS, for 72 h before experiments [27] , [28] . The determination of LDLr and LPR1r was performed by enzyme-linked immunoabsorbent assay (ELISA) kit as our previous report [25] . To further validate the selectivity of PPD NPs to cancerous and normal cells, we also measured the LDLr expression level on 3T3 cells.…”

Drug discovery and formulation development for acute pancreatitis

“…Suppressing these pro-inflammatory cytokines secretion has been recognized as a feasible strategy for pancreatitis treatment. HO-1 is the cytoprotective enzyme that controls inflammatory responses and redox homeostasis (Li et al., 2018 ). Induction of HO-1 pathway in early SAP could modulate the systemic inflammatory response and prevent liver injury via augmentation of IL-10 and inhibition of TNF-α (Zhang et al., 2017 ).…”