Photo-controlled Drug Delivery Research Articles

NIR‐Assisted MgO‐Based Polydopamine Nanoparticles for Targeted Treatment of Parkinson's Disease through the Blood–Brain Barrier (Adv. Healthcare Mater. 23/2022)

Parkinson's Disease In article 2201655, Yan-Qing Guan and co-workers successfully develop a novel photo-controlled drug delivery system for the treatment of Parkinson's disease. This nanoparticle uses MgO nanoparticles as a substrate, polydopamine as a shell and carries anti-SNCA plasmid and puerarin. Under the irradiation of 808 nm near-infrared light, the composite nanoparticles in deep tissues are activated, then absorbed by nerve cells after penetrating the blood–brain barrier, playing the role of antioxidation, anti-inflammation and inhibiting the accumulation of α-synuclein. Therefore, this strategy for intracerebral drug delivery can be an ideal approach to combat neurodegenerative diseases.

Liposome-based nanocomplexes with pH-sensitive second near-infrared photothermal property for combinational immunotherapy

Natural killer (NK) cell-mediated immunotherapy has shown a great promise for treatments of tumors, while some strategies that can improve its therapeutic efficacy and reduce potential adverse events are highly desired. We herein report a pH-sensitive second near-infrared (NIR-II) photothermal liposomal nanocomplex for enhanced NK cell-based immunotherapy of breast cancer. Such nanocomplex (LNCDS) consists of charge-transfer nanoparticles (CTN) with pH-sensitive NIR-II photothermal effect, deoxyribonuclease I (DNase I), NK cell stimulant (SIS3) and a surface coated thermal-responsive liposome shell. Upon 1064 nm laser irradiation, LNCDS generates mild heat in a controlled manner, which results in destruction of thermal-responsive liposome shell to allow on-demand release of stimulants and DNase I in tumor sites. The released DNase I not only kills cancer cells, but also induces immunogenic cell death (ICD), which synergizes with the action of the released SIS3 to promote activation of NK cells and cytotoxic T lymphocytes, contributing to enhanced therapeutic efficacy of immunotherapy. As a result, a single treatment of LNCDS upon NIR-II photoactivation greatly inhibits the growths of subcutaneously implanted primary and distant tumors in a breast cancer murine model, and even completely prevents lung metastasis. This study thus offers a photo-controlled drug delivery nanosystem for efficacy and precise NK cell-mediated immunotherapy of cancer.

(Photo)Thermal Stimulation of Functional Dithiolene Complexes in Soft Matter

Square‐planar bis(dithiolene) complexes are characterized with a planar delocalized structure and a strong and tunable near infrared (NIR) absorption; they are highly stable under laser irradiation, and their conversion efficiency (light to heat) reaches up to 40–50 %. Their involvement in soft matter, namely liquid crystals, gels, and nanoparticles, opens many possibilities to control the actual state of a material, particularly under light irradiation. Thus, liquid crystalline phases can easily be modified, (i) with temperature to modulate the extended magnetic interactions of paramagnetic complexes, or (ii) under laser irradiation to unravel these remarkable photothermal properties, toward the development of light‐responsive materials. Dithiolene complexes can be also functionalized to produce very effective gelation agents, while the photothermal effect can be used to destabilize at will their supramolecular organization. Besides photothermal therapy, new therapeutic agents were also developed for photo‐controlled drug delivery and bioimaging, combining chemotherapy and phototherapy. Hydrophobic complexes were accordingly designed for their encapsulation in block copolymer nanoparticles for photothermal therapy and photo‐controlled drug delivery under laser irradiation. This class of complexes can be also used as exogenous contrast agents for photoacoustic bioimaging.

Preparation of injectable hydrogel with near-infrared light response and photo-controlled drug release

Photo-controlled release hydrogel provides a new strategy for treating tumours. Under the stimulation of external light sources, the ability to release the entrapped drug on time and space on demand has outstanding advantages in improving drug utilisation, optimising treatment, and reducing toxicity and side effects. In this study, a photo-controlled drug delivery system for disulphide cross-linked polyaspartic acid (PASP-SS) hydrogels encapsulating proteinase K (ProK) adsorbed with platinum nanoparticles (PtNPs) was designed. The injectable cysteamine-modified polyaspartic acid (PASP-SH) sol and PtNPs adsorbed by ProK (ProK-PtNPs) as regulatory factors were prepared. Then, ProK-PtNPs and lentinan were dissolved in the sol, and the oxidant was added to the matrix to form the gel in situ quickly after injection. Finally, the degradation of PASP-SS hydrogel by ProK and the controllability of drug release under near-infrared (NIR) light irradiation were elucidated. In vitro degradation of hydrogels and drug release experiments showed that the degradation rate of PASP-SS hydrogel significantly increased and the drug release rate increased significantly under near-infrared radiation. The results of cytotoxicity test showed that PASP-SS, ProK-PtNPs, and lentinan all had more than 90% cell survival rate on NIH3T3, and the lentinan released from the carrier obviously inhibited the proliferation of MCF7. PASP hydrogel has the potential to respond to on-demand light control.

Progress in Research of Photo-controlled Drug Delivery Systems

Progress in Research of Photo-controlled Drug Delivery Systems

Photocontrolled micellar aggregation of amphiphilic DNA-azobenzene conjugates

We demonstrate the reversible micellar aggregation of a DNA-azobenzene conjugate in aqueous conditions, in which the photoisomerization of the initially apolar trans-azobenzene moiety to the polar cis isomer causes disassembly of the aggregates. The molecular basis for this phenomena is a change in the hydrophobic/hydrophilic balance of the conjugate as the more polar cis azobenzene isomer is formed upon exposure to 365nm irradiation. The conjugates were prepared by copper-free Click chemistry between an azide-modified, 53-base ssDNA and a cyclooctyne derivative of azobenzene. The photocontrolled aggregation of the conjugate was studied by dynamic light scattering and atomic force microscopy. The reversible micellar aggregation for a DNA-azobenzene conjugate has not been previously reported and holds promise for photocontrolled drug delivery applications.

An indicator-guided photo-controlled drug delivery system based on mesoporous silica/gold nanocomposites

A mesoporous silica/gold (MSN/Au) nanocomposite was designed for photo-controlled drug delivery targeted specifically at tumor cells. The MSN/Au nanocomposite was composed of MSN-based drug carriers and gold nanoparticle (AuNP)-based indicators. While the MSN-based drug carrier was a mesoporous silica nanoparticle immobilized with photo-switchable azobenzene (Azo) moieties, the AuNP-based indicator was a fluorescence-quenched AuNP modified with a matrix metalloproteinase (MMP) substrate and poly(ethylene glycol). The two kinds of nanoparticles were connected by an α,β cyclodextrin (α,β CD) dimer “bridge.” In vitro studies demonstrated that the nanocomposite specifically interacted with tumor sites overexpressing MMP-2, which enabled guidance of the subsequent UV light irradiation for releasing entrapped drugs. Through integration of the AuNP-based indicator and the MSN-based drug carrier, the MSN/Au nanocomposite could precisely localize the released drug to tumor sites, thereby significantly improving therapeutic efficacy.

Photoisomerization Quantum Yield of Azobenzene-Modified DNA Depends on Local Sequence

Photoswitch-modified DNA is being studied for applications including light-harvesting molecular motors, photocontrolled drug delivery, gene regulation, and optically mediated assembly of plasmonic metal nanoparticles in DNA-hybridization assays. We study the sequence and hybridization dependence of the photoisomerization quantum yield of azobenzene attached to DNA via the popular d-threoninol linkage. Compared to free azobenzene we find that the quantum yield for photoisomerization from trans to cis form is decreased 3-fold (from 0.094 ± 0.004 to 0.036 ± 0.002) when the azobenzene is incorporated into ssDNA, and is further reduced 15-fold (to 0.0056 ± 0.0008) for azobenzene incorporated into dsDNA. In addition, we find that the quantum yield is sensitive to the local sequence including both specific mismatches and the overall sequence-dependent melting temperature (Tm). These results serve as design rules for efficient photoswitchable DNA sequences tailored for sensing, drug delivery, and energy-harvesting applications, while also providing a foundation for understanding phenomena such as photonically controlled hybridization stringency.

Phototriggered release of photolabile drugs via two‐photon absorption‐induced cleavage of polymer‐bound dicoumarin

Abstract7‐(tert‐Butyldimethylsiloxy)‐7′‐(methacryloxy)dicoumarin (TBS‐Cum‐D‐MA) is introduced as a versatile polymerizable and photocleavable linker system for drug attachment to acrylic polymers. Following the copolymerization of the TBS‐Cum‐D‐MA with monomeric methylmethacrylate, a model drug chlorambucil was attached in a simple reaction. Phototriggered drug release via single‐ and two‐photon absorption induced cycloreversion of the cyclobutane of the dicoumarin part was investigated. The bound drug chlorambucil is sensitive to UV light being required for single‐photon induced cleavage of the dicoumarin linker and decomposes upon UV exposure. However, under the conditions of two‐photon absorption induced drug release, no photodegradation of chlorambucil was observed. As the only effective two‐photon absorber in the molecule is the cyclobutane structure, even high energies of visible light do not cause any degradation of the drug. This suggests that two‐photon‐triggered drug release may be successfully accomplished even with UV light sensitive drugs. The concept introduced here may be a powerful strategy in polymer design for photocontrolled drug delivery devices. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 2443–2452, 2007

Photodimerized 7-hydroxycoumarin with improved solubility in PMMA: Single-photon and two-photon-induced photocleavage in solution and PMMA films

tert-Butyldimethylsilyl-chloride (TBS) revealed to be a photostable protecting group for the photodimerization of 7-hydroxycoumarin in a [2 + 2]-cycloaddition. TBS-functionalized coumarin dimers show an about 100-fold increased solubility in organic solvents enabling them to be easily incorporated into polymeric films, e.g., PMMA. In the described photochemical dimerization reaction almost pure anti-head-to-head isomer is obtained. The single- and two-photon absorption-induced cycloreversion reactions in acetonitrile as well as in PMMA matrix were investigated and the two-photon absorption cross sections and quantum yields were determined to be around 1 GM and about 0.36, respectively. The only product obtained upon photocleavage of the dimer is the TBS-protected 7-hydroxycoumarin monomer. The TBS-protecting group withstands the high light intensities required for two-photon absorption-induced photocleavage without any noticeable degradation. The mild deprotection conditions for tert-butyldimethylsilyl-ethers (TBS-ethers), the chemical stability of the compound as well as its significantly improved solubility in organic solvents and its miscibility with acrylic polymers, make this a very useful compound for potential applications in 3D volumetric optical data storage and photocontrolled drug delivery.

PEG-modified gold nanorods with a stealth character for in vivo applications

Gold nanorods prepared in hexadecyltrimethylammonium bromide (CTAB) solution are expected to provide novel materials for photothermal therapy and photo-controlled drug delivery systems. Since gold nanorods stabilized with CTAB show strong cytotoxicity, we developed a technique to modify these with polyethyleneglycol (PEG) for medical applications. PEG-modification was achieved by adding mPEG-SH in the CTAB solution, then, excess CTAB was removed by dialysis. PEG-modified gold nanoparticles showed a nearly neutral surface, and had little cytotoxicity in vitro. Following intravenous injection into mice, 54% of injected PEG-modified gold nanoparticles were found in blood at 0.5 h after intravenous injection, whereas most of gold was detected in the liver in the case of original gold nanorods stabilized with CTAB.