A facile modular approach toward multifunctional supramolecular polyplexes for targeting gene delivery

Abstract

A convenient modular approach for multifunctional supramolecular self-assembly polyplexes of poly(cyclodextrin) and mono-adamantane-terminated guest polymers displaying targeting cellular uptake and transfection.

Supramolecular Modular Approach toward Conveniently Constructing and Multifunctioning a pH/Redox Dual-Responsive Drug Delivery Nanoplatform for Improved Cancer Chemotherapy

“…Active targeting ligands are widely employed to enhance cell selectivity and cellular internalization of nanosized DDSs . Two target molecules, LA- or FA-terminated Ad-PEG (Ad-PEG-LA and Ad-PEG-FA), which were demonstrated to form noncovalent bonds with PCD by self-assembly, , were chosen to functionalize PRMSNs via the host–guest interactions between PCD and Ad groups. The Ad-terminated PEG (Ad-PEG) was used as a control.…”

“…DOX hydrochloride was purchased from Meilun Biology Technology Co., Ltd (Dalian, China). Poly­(β-CD) (PCD), Ad-terminated poly­(ethylene glycol) (Ad-PEG), Ad- and folate-terminated PEG (Ad-PEG-FA), Ad- and lactobionic-acid-terminated PEG (Ad-PEG-LA), and Ad-terminated polyethylenimine (Ad-PEI) were synthesized in previous works. , Ad-terminated FITC (Ad-FITC) was synthesized as in the literature …”

Paclitaxel prodrug based mixed micelles for tumor-targeted chemotherapy

“…The introduction of FA offers the possibility to active targeting cancers with an enhanced antitumor efficacy that has been employed and conrmed by many previous reports. 29,30 Herein, the MMs formed by a rational mixture of DSPE-PEG-FA with PTX-PEG were expected to combine both passive and active targeting abilities to elevate the antitumor efficacy as compared to the SMs.…”

A Sequentially Responsive Nanosystem Breaches Cascaded Bio-barriers and Suppresses P-Glycoprotein Function for Reversing Cancer Drug Resistance

“…P-glycoprotein (P-gp), an ATP-dependent efflux pump, is overexpressed in MCF7/ADR cells, inhibiting drug accumulation in cancer cells to cause multidrug resistance . PEI reportedly reduces mitochondrial membrane potential and impairs mitochondrial respiration, thereby depleting ATP production. , Thus, we synthesized a PEI derivative (CD-PEI) as the gatekeeper of PRMSNs using a low cytotoxic PEI (1.8 kDa), and we hypothesized that RCMSNs might impair the efflux function of P-gp via suppressing intracellular ATP supply, thus facilitating drug resistance reversal. Supporting this notion, the mitochondrial crista structures disappeared in MCF7/ADR cells after RCMSNs treatment, as shown in the TEM images (Figure A and Figure S7).…”

“…To breach CAPIR, camouflaging nanosystems with stealth coronas composed of neutral or negative polymers, such as poly­(ethylene glycol) (PEG), could be an effective strategy to prevent rapid clearance of nanosystems, offering the sufficient amount of time for nanosystems to enter tumors. , However, the stealth effect of PEG shielding also impedes cancer cells’ uptake of nanoparticles, undesirably reducing drug delivery efficacy. , One possible way to reconcile the above two conflicting (alleged PEG-dilemma) needs could be to modify the nanoparticles with a cationic surface set to be exposed after PEG detachment . Being affinitive to negatively charged cancer cell membranes, this cationic surface would facilitate efficient cellular uptake of nanoparticles − and enhance their tumor penetration, as previously demonstrated. , Among various cationic polymers, polyethyleneimine (PEI) is unique as it can depolarize mitochondria and disrupt their respiration, consequently reducing ATP production, which in turn impairs P-gp’s ATP-dependent drug-efflux activity. − Thus, we hypothesized that a PEI-based nanocarrier wrapped with detachable PEG “camouflage” would effectively breach the cascaded bio-barriers, and PEI as the nanocarrier’s structural component could also functionally suppress P-gp’s efflux activity for overcoming drug resistance.…”