Success of chemotherapy as a treatment for cancer has been often inhibited by multidrug resistance (MDR) of the cancer cells. There is a clear need to generate strategies to overcome this resistance. In this work, we have developed redox-responsive and core-cross-linked micellar nanocarriers using poly(ethylene glycol)-block-poly(2-(methacryloyloxy)ethyl 5-(1,2-dithiolan-3-yl)pentanoate) diblock copolymers (PEG-b-PLAHEMA) with tunable swelling properties for the delivery of drugs toward drug-sensitive MDA-MB-231 and drug-resistant MDA-MB-231 (231R) cancer cells. PEG-b-PLAHEMA containing varying number of 2-(methacryloyloxy)ethyl 5-(1,2-dithiolan-3-yl)pentanoate (LAHEMA) units were synthesized by employing the reversible addition-fragmentation chain transfer polymerization technique. The block copolymer self-assembly, cross-linking induced by reduction, and de-cross-linking triggered time-dependent controlled swelling of micelles were studied using dynamic light scattering, fluorescence spectroscopy, and transmission electron microscopy. In vitro cytotoxicity, cellular uptake efficiency, and glutathione-responsive anticancer activity of doxorubicin (DOX) encapsulated in core-cross-linked block copolymer micelles (CCMs) toward both drug-sensitive and drug-resistant cancer cell lines were evaluated. Significant reduction in IC was observed by DOX-loaded CCMs toward drug-resistant 231R cancer cell lines, which was further improved by coencapsulating DOX and verapamil (a P-glycoprotein inhibitor) in CCMs. Thus, these reduction-sensitive biocompatible CCMs with tunable swelling property are very promising in overcoming MDR in cancer cells.
The ability to regulate the formation of nanostructures through self-assembly of amphiphilic block copolymers is of immense significance in the field of biology and medicine. In this work, a new block copolymer synthesized by using reversible addition-fragmentation chain transfer (RAFT) polymerization technique from poly(ethylene glycol) monomethyl ether acrylate (PEGMA) and Boc-l-tryptophan acryloyloxyethyl ester (Boc-l-trp-HEA) was found to spontaneously form pH-responsive water-soluble nanostructures after removal of the Boc group. While polymer vesicles or polymerosomes were formed at physiological pH, the micelles were formed at acidic pH (< 5.2), and this facilitated a pH-induced reversible vesicle-to-micelle transition. Formation of these nanostructures was confirmed by different characterization techniques, viz. transmission electron microscopy, dynamic light scattering, and steady-state fluorescence measurements. Further, these vesicles were successfully utilized to reduce HAuCl4 and stabilize the resulting gold nanoparticles (AuNPs). These AuNPs, confined within the hydrophobic shell of the vesicles, could participate in energy transfer process with fluorescent dye molecules encapsulated in the core of the vesicles, thus forming a nanometal surface energy transfer (NSET) pair. Subsequently, following the efficiency of energy transfer between this pair, it was possible to monitor the process of transition from vesicles to micelles. Thus, in this work, we have successfully demonstrated that NSET can be used to follow the transition between nanostructures formed by amphiphilic block copolymers.
This paper demonstrates the photophysics of curcumin inside polymeric nanoparticles (NPs), which are being recently used as targeted drug delivery vehicles. For this purpose, we have prepared three polymeric NPs by ultrasonication method from three well-defined water-insoluble random copolymers. These copolymers having various degrees of hydrophobicity were synthesized via reversible addition-fragmentation transfer (RAFT) method using styrene and three different functional monomers, namely, 2-hydroxyethyl acrylate, 4-formylphenyl acrylate, and 4-vinylbenzyl chloride. The photophysics of the curcumin molecules inside the polymeric NPs have been monitored by applying tools like steady state and time-resolved fluorescence spectroscopy. An increase in fluorescence intensity along with an increase in the lifetime values indicated a perturbation of the excited state intramolecular proton transfer (ESIPT) process of curcumin inside the polymeric NPs.
Iodinium cation (I(+) or IOAc) was produced from the combination of phenyliodine diacetate (PIDA) and iodine. I(+) facilitated the direct vicinal difunctionalization of olefins to α-azido, α-trideuteriomethoxy, α-2,2,2-trifluoroethoxy and α-acyloxy alkyl iodides via cation-π interaction at room temperature and under transition-metal free conditions.
The discovery of a direct method for the synthesis of three-ring heterocyclic carbazoles from unactivated arenes and anilides by a metal-free (organic) intermolecular dehydrogenative annulation reaction under ambient laboratory conditions is reported. Iodine(III) was used as the sole reagent either stoichiometrically from inexpensive phenyliodine diacetate or organocatalytically by in situ generation from PhI-mCPBA. In a single step, three C(sp)-H bonds and one N(sp)-H bond are functionalized from two different arenes for tandem C-C and C-N bond formation reactions.
Hypervalent iodine compounds are known for their extensive use as potentialo xidants in organic synthesis.I ns pite of the similar reactivity with transitionm etals,h ypervalent iodine reagents are more preferred because of their environmental sustainability.A mong several types of hypervalent iodine reagents,t rivalent organoiodine(III) reagents are highly popular due to their easy accessibility,s tability and controlled oxidizing reactivity.A lso, iodine(III) reagents are commerciallya vailable andi nexpensive. Amines and amidesr eact with iodine(III) oxidants in some specificw ay to provide ad ivalent electrophilic ionic species known as an itrenium ion. Depending on the nature and stability of the nitrenium ion, numerous oxidative transformations to generate valuable functional molecules have been reported.T his review encompassesd iscussionsa bout hypervalent organo iodine(III)-enabled organic transformationsw ith the involvemento fanitrenium ion as an intermediate. Figure1.Ionic electrophilic speciesw ith 6v alance electrons.
An intermolecular dehydrogenative annulation (IDA) for carbazole synthesis via sequential C-C/C-N bond formation with a selective alkyl group migration is reported. Using the hypervalent iodine(III) reagent PhI(OAc) (PIDA), in a one-pot operation, up to five C(sp2)-H bonds, one N(sp3)-H bond functionalization, and one alkyl (Me, Et) group migration could all be achieved from non-prefunctionalized 1,3,5-trialkylbenzenes and anilides under ambient laboratory conditions. Mechanistically, it is shown that PIDA reacts with anilides to generate a nitrenium ion or an equivalent carbenium ion which influences the second aromatic ring to be activated for C-C/C-N bond formation. Strategically, regioselective fusion of arenes to anilides is described.
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