Photocontrolled Release of the Anticancer Drug Chlorambucil with Caged Harmonic Nanoparticles

Abstract

Dedicated to Philippe Renaud on the occasion of his 60th birthdayWhile chemotherapy is one of the most used treatments in oncology, the systemic administration of chemotherapeutics generally results in undesired damages to healthy tissues and cells, side effects such as severe nausea and leukopenia, and reduced efficacy due to multidrug resistance and poor target accessibility. The limitations of conventional chemotherapy formulation have prompted the development of alternative nanomaterials-based strategies to achieve targeted and stimuli sensitive payload delivery to reach optimal local drug concentration at tumor sites. In this study, the anticancer drug chlorambucil (Clb) was conjugated to the surface of silica coated lithium niobate (LNO) harmonic nanoparticles (HNPs) using a photocaging tether based on coumarin-4-yl methyl derivative. Upon laser pulsed femtosecond irradiation at 790 nm, the second harmonic emission from the metal oxide core induced the efficient release of Clb, with concomitant contribution from the nonlinear absorption of the coumarin (CM)-based moiety.

On the Reaction Pathways and Growth Mechanisms of LiNbO3 Nanocrystals from the Non-Aqueous Solvothermal Alkoxide Route

“…However, because of their colloidal stability and reduced size and shape distributions, such samples can be implemented as new calibration probes for second harmonic spectroscopic studies over broad excitation ranges thanks to the absence of size and shape effects in the orientation-averaged second-order susceptibility of sub-50 nm LN nanocrystals and to their inherent non-resonant SHG response [ 17 , 21 ]. After surface functionalization, advanced theranostic applications based on the SH properties of LN nanocrystals have also been recently demonstrated for the controlled and local release of the anticancer drug chlorambucil [ 69 ]. Noteworthy, in this study, the systematic variation of the reaction medium composition allowed us to suggest a reaction pathway on the basis of the available literature data addressing the thermal stability of niobium alkoxides.…”

Photoactivation Strategies for Therapeutic Release in Nanodelivery Systems

“…[119] These micelles showed degradation upon irradiation at 365 nm (ONB) or 470-490 nm (BODIPY), which was attributed to photolytic degradations at the hydrophobic core. [23,169] UCN@G5(FA)-DOX DOX TNB (980) [ 142] UCN@DOX DOX ONB (980) [ 171] AuNP@5-FU 5-FU ONB (365) [ 140] QD@5-FU 5-FU N-Methyl-4-picolinium (Vis) [ 118] Poly(methacrylate) micelle 5-FU [2+2] Addition (254) [ 176] RNA nanocage Paclitaxel ONB [ 181] Polymer micelle Camptothecin ONB [ 182] Poly(l-lysine) Chlorambucil Pyrene (365) [ 183] NP aggregate Chlorambucil Acridin-9-methanol (410) [ 131] Mesoporous silica nanocapsule Chlorambucil Coumarin (650) [ 184] LiNbO 3 Chlorambucil Coumarin (790) [ 111] Human serum albumin Pt(II) Pt(IV) azide [ 185] Polymer micelle Pt(II) Pt(IV) azide [ 186,187] UCN@Pt(IV) Pt(II) Pt(IV) (980) [ 174] Antibacterial PEG hydrogel Ciprofloxacin ONB (365) [ 189] G5(PMB)(Cipro) Ciprofloxacin ONB (365) [ 172] Nucleotide AuNP@dsDNA dsDNA ONB (350) [ 191] AgNP@DNA Antisense DNA ONB [ 192] UCN@RNA Cas9-sgRNA ONB (980) [ 193] Gas Molecule -CD polymer NO Nitroaniline (400) [ 195] QD@nitroaniline NO Nitroaniline (350, 800) [ 196] NanoTiO 2 NO Ru-NO (400) [ 197] Graphene QD NO Ru-NO (808) [ 198] UCN@(Mn-CO) CO Mn-CO (980) [ 199] UCN@thiophenedioxide SO 2 Thiophenedioxide (980) [ 175] UCN@H 2 S precursor H 2 S ONB (980) [ 200] Polymer micelle disassembly is applied in a similar manner for drug delivery as demonstrated by DOX release from micelles prepared with ONB-caged amphiphilic block copolymer [208] or poly(acrylate) ester copolymers. [207] Micelle disassembly generally occurs regardless of its shape or surface functionalization.…”

Gold-seeded Lithium Niobate Nanoparticles: Influence of Gold Surface Coverage on Second Harmonic Properties

“…Among them, the piezoelectric, electro-optic and nonlinear optical properties are all due to its non-centrosymmetric crystalline structure. Interestingly, the absence of phase-matching conditions at the nanoscale for the so-called harmonic NPs, paved the way to new bio-imaging [ 12 ] and photo-triggering [ 13 ] approaches when LN NPs, for instance, are used as exogenous biomarkers. In terms of measurable nonlinear optical signals, a very rich multi-order response has recently been measured with the simultaneous detection of ten distinct emissions spanning from the deep ultraviolet to the short-wave infrared region [ 14 ].…”