Multifunctional TiO2/C nanosheets derived from 3D metal-organic frameworks for mild-temperature-photothermal-sonodynamic-chemodynamic therapy under photoacoustic image guidance.

Going below and beyond the surface: Microneedle structure, materials, drugs, fabrication, and applications for wound healing and tissue regeneration

Titanium-based nanomaterials for cancer theranostics

Conventional cancer treatment modalities are often associated with major therapeutic limitations and severe side effects. Photodynamic therapy is a localized noninvasive mode of treatment that has given a different direction to cancer research due to its effectivity against a wide range of cancers and minimal side effects. A photosensitizer is the key component of photodynamic therapy (PDT) that generates cytotoxic reactive oxygen species to eradicate cancer cells. As the therapeutic effectivity of PDT greatly depends upon the photosensitizer, great efforts have been made to search for an ideal photosensitizer. Chlorin e6 is a FDA approved second generation photosensitizer that meets the desired clinical properties for PDT. It is known for its high reactive oxygen species (ROS) generation ability and anticancer potency against many types of cancer. Hydrophobicity is a major drawback of Ce6 that leads to its poor biodistribution and rapid clearance from the circulatory system. To overcome this drawback, researchers have designed and fabricated several types of nanosystems, which can enhance Ce6 solubility and thereby enhance its bioavailability. These nanosystems also improve tumor accumulation of Ce6 by selectively targeting the cancer cells through passive and active targeting. In addition, Ce6 has been employed in many combination therapies like chemo-photodynamic therapy, photoimmunotherapy, and combined photodynamic-photothermal therapy. A combination therapy is more curative than a single therapy due to the synergistic effects of individual therapies. Ce6-based nanosystems for combination therapies have shown excellent results in various studies and provide a promising platform for cancer treatment.

Chlorin e6: A Promising Photosensitizer in Photo-Based Cancer Nanomedicine.

Wound healing is a largely unmet medical issue in trauma, burn, and diabetes. In this study, a pullulan-based and nanoparticle-loaded smart microneedle patch is designed to release drugs differentially based on the needs of wound healing. Chitosan and fucoidan are first used to prepare moxifloxacin (MOX)-loaded nanoparticles (MOXNPs) with a diameter of 258.0 ± 10.86 nm, PDI 0.19 ± 0.06, and surface charge 45.1 ± 3.9 mV. MOXNPs, lidocaine (LH), and thrombin (TH) are then incorporated to a 30 % (w/w) pullulan-based microneedle patch (TH + LH + MOXNPs@MN). TH + LH + MOXNPs@MN possesses uniform and cone-shaped microneedles with a length of 725 μm, demonstrating good biocompatibility, sufficient strength for skin penetration, fast skin dissolution within 55 ± 5 min, rapid release of TH and LH within 1 h, and sustained release of MOX for 24 h. TH + LH + MOXNPs@MN heals mice skin wounds completely within 7 days and restores collagen deposition with accelerated cell proliferation, granulation, and reduced pro-inflammatory cytokines. In conclusion, this study utilizes combined polysaccharides to develop a smart multifunctional microneedle platform that achieves rapid hemostasis/analgesia and sustained bactericidal action. The smart and combined therapy is a potential strategy for high-quality wound healing.

A chitosan/fucoidan nanoparticle-loaded pullulan microneedle patch for differential drug release to promote wound healing.

Oxygen deficient TiO2-x nanoparticles (NPs) have been recognized as a category of new-fashioned photothermal agents to offer safer PTT. However, the surface of TiO2-x NPs is deficient in free active groups or radicals to conjugate functional therapeutic molecules, which seriously impedes their in-depth development for versatile medical applications. In this study, surface activation of TiO2-x NPs was realized by the facile conjugation of (3-aminopropyl)triethoxysilane (APTES) through the formation of a stable Si-O-Ti bond, and photosensitizer chlorin e6 (Ce6) was successfully modified onto the TiO2-x NP surface and with a considerably high loading content. The resultant TiO2-x@APTES/Ce6 (TAC) NPs displayed decent biosafety, rapid tumor enrichment and outstanding performance in photoacoustic (PA) imaging. Taking advantage of the intense photo-absorption in the near-infrared (NIR) region and high dose of conjugated Ce6, a powerful antitumor effect was realized based on the combination of hyperthermia-induced cell ablation and cytotoxic reactive oxygen species (ROS)-triggered apoptosis both in vitro and in vivo. Moreover, PA imaging guidance was exceptionally useful for locating the tumor position and optimizing the treatment regimens. Apart from Ce6, this elaborate modification strategy for TiO2-x is believed to be universal for steadily binding more versatile therapeutic agents, which would definitely favor the development of multifunctional TiO2-x-based nanocomplexes for enhanced tumor treatment.

Rational design of oxygen deficient TiO2-x nanoparticles conjugated with chlorin e6 (Ce6) for photoacoustic imaging-guided photothermal/photodynamic dual therapy of cancer.

Skin infections caused by pathogens, including bacteria, fungi and viruses, are difficult to completely eliminate through standard topical administration, owing to the restricted drug permeation into the epidermis layer. Herein, we developed a poly(ethylene glycol) diacrylate (PEGDA) microneedle patch with surface coating of a nanosilver (NS) encapsulated gelatin/sucrose film for antibacterial applications, by virtue of enhanced skin permeation by microneedle penetration and efficient drug delivery through rapid film dissolving. NS was facilely synthesized through a green process based on the bioinspired crystallization of ionic state silver in the presence of a silk fibroin (SF) template. A gelatin/sucrose polymeric film encapsulating NS was dressed on the surface of the mold cavity, and film-coated PEGDA (PEGDA/film-NS) microneedles were subsequently fabricated through standard ultraviolet (UV) light-induced polymerization. To demonstrate their advantages for therapeutic applications, the physicochemical properties of the as-developed microneedles were characterized in terms of their morphology, composition, mechanical strength, etc. Moreover, rapid NS release from PEGDA@film-NS microneedles driven by the aqueous environment was demonstrated under physiological conditions. Additionally, such film-coated microneedles exhibited good mechanical strength for skin penetration, and their antibacterial activity against Gram-positive bacteria (Staphylococcus epidermidis and Staphylococcus aureus) as well as Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) was verified using bacterial suspension in vitro. Altogether, such a minimally invasive strategy exhibited good potential for realizing a broad-spectrum antibacterial effect, which may provide a practical methodology for the management of polymicrobial skin infection during clinical trials.

Intradermal administration of green synthesized nanosilver (NS) through film-coated PEGDA microneedles for potential antibacterial applications.

Two-dimensional Bi2Te3 nanosheets (NSs) have recently been validated as a new type of photothermal agent to provide an alternative option for tumor ablation via light-induced hyperthermia. However, the surface of Bi2Te3 NSs lacks active radicals for the conjugation of functional molecules, which undoubtedly impedes their versatile utilization in medical areas. Here, the surface activation of Bi2Te3 NSs was accomplished via the in situ growth of an SiO2 nanoshell assisted by tetraethyl orthosilicate (TEOS). Upon the co-condensation of (3-aminopropyl)triethoxysilane (ATPES), terminal amino groups (-NH2) were generated on the surface of the Bi2Te3@SiO2 NSs, which were further covalently coupled with the photosensitizer chlorin e6 (Ce6) through a standard amide reaction. The resultant Bi2Te3@SiO2/Ce6 (BSC) NSs displayed admirable photothermal properties, a high Ce6 loading capacity, and good biocompatibility. Upon dual-wavelength laser irradiation, an excellent tumor suppression effect arising from thermal ablation and reactive oxygen species (ROS)-induced apoptosis was verified both in cell experiments and in animal studies. In addition, synchronous fluorescence/photoacoustic/infrared (FL/PA/IR) tri-modal imaging could provide useful information for both tumor diagnosis and prognosis. Overall, this facile strategy for the activation of Bi2Te3 is regarded to be universal for the development of more versatile Bi2Te3-based nanoplatforms, which should favor the rapid diagnosis and effective treatment of fatal diseases.

The synthesis of two-dimensional Bi 2 Te 3 @SiO 2 core–shell nanosheets for fluorescence/photoacoustic/infrared (FL/PA/IR) tri-modal imaging-guided photothermal/photodynamic combination therapy

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Rational design of oxygen deficient TiO2-x nanoparticles conjugated with chlorin e6 (Ce6) for photoacoustic imaging-guided photothermal/photodynamic dual therapy of cancer.

Intradermal administration of green synthesized nanosilver (NS) through film-coated PEGDA microneedles for potential antibacterial applications.

The synthesis of two-dimensional Bi 2 Te 3 @SiO 2 core–shell nanosheets for fluorescence/photoacoustic/infrared (FL/PA/IR) tri-modal imaging-guided photothermal/photodynamic combination therapy