Phototriggered Secretion of Membrane Compartmentalized Bioactive Agents

Abstract

A strategy for the light-activated release of bioactive compounds (BODIPY, colchicine, paclitaxel, and methotrexate) from membrane-enclosed depots is described. We have found that membrane permeable bioagents can be rendered membrane impermeable via covalent attachment to cobalamin (Cbl) through a photo-cleavable linker. These Cbl-bioagent conjugates are imprisoned within lipid-enclosed compartments in the dark, as exemplified by their retention in the interior of erythrocytes. Subsequent illumination drives the secretion of the bioactive species from red blood cells. Photo-release is triggered by wavelengths in the red, far red and near IR, which can be pre-assigned by affixing a fluorophore with the desired excitation wavelength to the Cbl-bioagent conjugate. Pre-assigned wavelengths allow different biologically active compounds to be specifically and unambiguously photo-released from common carriers.

On Command Drug Delivery via Cell‐Conveyed Phototherapeutics

“…The Cy5–B12‐TAX conjugate 2 was prepared from a chemically modified derivative of B12 ( 1 ) . In brief, the three‐step procedure includes condensation of N‐Deboc docetaxel with the free carboxylate of 1 , removal of the Fmoc protecting group, and a final condensation of the exposed amine with the N‐hydroxysuccinimide activated form of Cy5 (Scheme S1, Figure S1, Supporting Information) . Alkyl‐cobalamins are photolyzed only at the wavelengths absorbed by the corrin ring (330–575 nm).…”

Shining a Light on Bioorthogonal Photochemistry for Polymer Science

“…[118] Rational redesign, to attach the fluorophore antenna to the hydroxy group on the ribose ring of vitamin-B12, allowed for attachment of therapeutics to the photocleavable position to produce pro-drugs and nanotherapeutics. [119,120] The phototriggered release of alkyl radicals from the Co-C of vitamin B12 bond has also been exploited for the photopolymerization of hydrogels, to encapsulate live cells. [121] The radical system demonstrated that far-red absorbing photoinitiators Reproduced with permission.…”

Harnessing Biology to Deliver Therapeutic and Imaging Entities via Cell‐Based Methods

“…Echogenic polymer bubbles andD OX-loaded vesicless usceptible to focusedu ltrasound liberation, co-delivered in macrophages,r esulted in substantialt umor uptake, while free NP-DOX largely accumulated in the liver;t he cell-based agents penetrated 150 mmf rom the nearest blood vessel, however NPs were limited to 10-15 mm. [22] Photo-release of drugs has been used with red, farred, and near-IR light in erythrocytes, [24,63] which can uptake entitiesa sd escribed in further detail below.I ron oxide nanoparticles phagocytosed by macrophages can also assist in "directing" cellular delivery via magnetic resonance imaging [64] or electromagnetic actuation. [65] Cargo-bearing cells loaded in this manner have been utilized to cross the blood-brain-barrier.I nt he delivery of drug-laden nanoparticles for the treatmento fg lioma, macrophage viability was not affected at doxorubicin concentrations up to 25 mgmL À1 and drug-loaded nanoparticles exhibited better tumor targetinge fficiency and penetration.…”

“…HD has been employed to load therapeutic enzymes, [27,67] nanoparticles, [48] and drugs. [63,68] These same ("blood-banking") conditions are also used for blood storage and transfusion. An apparatus, termed a" Red Cell Loader" (Sorin Group, Italy) has been developed to automate the process, and used to encapsulate av ariety of drugs.…”

“…Echogenic polymer bubbles and DOX‐loaded vesicles susceptible to focused ultrasound liberation, co‐delivered in macrophages, resulted in substantial tumor uptake, while free NP‐DOX largely accumulated in the liver; the cell‐based agents penetrated 150 μm from the nearest blood vessel, however NPs were limited to 10–15 μm . Photo‐release of drugs has been used with red, far‐red, and near‐IR light in erythrocytes, which can uptake entities as described in further detail below. Iron oxide nanoparticles phagocytosed by macrophages can also assist in “directing” cellular delivery via magnetic resonance imaging or electromagnetic actuation …”