Arif Gulzar

Stimuli responsive drug delivery application of polymer and silica in biomedicine

In the last decade, using polymer and mesoporous silica materials as efficient drug delivery carriers has attracted great attention. Although the development and application of them involves some inevitable barriers, such as chronic toxicities, long-term stability, understanding of the biological fate and physiochemical properties, biodistribution, effect in the biological environment, circulation properties and targeting efficacy in vivo. The construction of stimuli responsive drug carriers using biologically safe materials, followed by hydrophilic modification, bioconjugation, targeting functionalization, and detailed safety analysis in small/large animal models may be the best way to overcome these barriers. Huge progress has been made in stimuli responsive drug delivery systems based on polymer and mesoporous silica materials, mainly including pH-, thermo-, light-, enzyme-, redox-, magnetic field- and ultrasound-responsive drug delivery systems, all of which are highlighted in this review.

Integration of IR-808 Sensitized Upconversion Nanostructure and MoS2 Nanosheet for 808 nm NIR Light Triggered Phototherapy and Bioimaging

Near infrared (NIR) light triggered phototherapy including photothermal therapy (PTT) and photodynamic therapy (PDT) affords superior outcome in cancer treatment. However, the reactive oxygen species (ROS) generated by NIR-excited upconversion nanostructure is limited by the feeble upconverted light which cannot activate PDT agents efficiently. Here, an IR-808 dye sensitized upconversion nanoparticle (UCNP) with a chlorin e6 (Ce6)-functionalized silica layer is developed for PDT agent. The two booster effectors (dye-sensitization and core-shell enhancement) synergistically amplify the upconversion efficiency, therefore achieving superbright visible emission under low 808 nm light excitation. The markedly amplified red light subsequently triggers the photosensitizer (Ce6) to produce large amount of ROS for efficient PDT. After the silica is endowed with positive surface, these PDT nanoparticles can be easily grafted on MoS2 nanosheet. As the optimal laser wavelength of UCNPs is consistent with that of MoS2 nanosheet for PTT, the invented nanoplatform generates both abundant ROS and local hyperthermia upon a single 808 nm laser irradiation. Both the in vitro and in vivo assays validate that the innovated nanostructure presents excellent cancer cell inhibition effectiveness by taking advantages of the synergistic PTT and PDT, simultaneously, posing trimodal (upconversion luminescence/computed tomography (CT)/magnetic resonance imaging (MRI) imaging capability.

Bioapplications of graphene constructed functional nanomaterials

Graphene has distinctive mechanical, electronic, and optical properties, which researchers have applied to develop innovative electronic materials including transparent conductors and ultrafast transistors. Lately, the understanding of various chemical properties of graphene has expedited its application in high-performance devices that generate and store energy. Graphene is now increasing its terrain outside electronic and chemical applications toward biomedical areas such as precise bio sensing through graphene-quenched fluorescence, graphene-enhanced cell differentiation and growth, and graphene-assisted laser desorption/ionization for mass spectrometry. In this Account, we evaluate recent efforts to apply graphene and graphene oxides (GO) to biomedical research and a few different approaches to prepare graphene materials designed for biomedical applications and a brief perspective on their future applications. Because of its outstanding aqueous processability, amphiphilicity, surface functionalizability, surface enhanced Raman scattering (SERS), and fluorescence quenching ability, GO chemically exfoliated from oxidized graphite is considered a promising material for biological applications. In addition, the hydrophobicity and flexibility of large-area graphene synthesized by chemical vapor deposition (CVD) allow this material to play an important role in cell growth and differentiation. Graphene is considered to be an encouraging and smart candidate for numerous biomedical applications such as NIR-responsive cancer therapy and fluorescence bio-imaging and drug delivery. To that end, suitable preparation and unique approaches to utilize graphene-based materials such as graphene oxides (GOs), reduced graphene oxides (rGOs), and graphene quantum dots (GQDs) in biology and medical science are gaining growing interest.

Au Nanoclusters Sensitized Black TiO2−x Nanotubes for Enhanced Photodynamic Therapy Driven by Near-Infrared Light

The low reactive oxygen species production capability and the shallow tissue penetration of excited light (UV) are still two barriers in photodynamic therapy (PDT). Here, Au cluster anchored black anatase TiO2-x nanotubes (abbreviated as Au25 /B-TiO2-x NTs) are synthesized by gaseous reduction of anatase TiO2 NTs and subsequent deposition of noble metal. The Au25 /B-TiO2-x NTs with thickness of about 2 nm exhibit excellent PDT performance. The reduction process increased the density of Ti3+ on the surface of TiO2 , which effectively depresses the recombination of electron and hole. Furthermore, after modification of Au25 nanoclusters, the PDT efficiency is further enhanced owing to the changed electrical distribution in the composite, which forms a shallow potential well on the metal-TiO2 interface to further hamper the recombination of electron and hole. Especially, the reduction of anatase TiO2 can expend the light response range (UV) of TiO2 to the visible and even near infrared (NIR) light region with high tissue penetration depth. When excited by NIR light, the nanoplatform shows markedly improved therapeutic efficacy attributed to the photocatalytic synergistic effect, and promotes separation or restrained recombination of electron and hole, which is verified by experimental results in vitro and in vivo.

Lanthanide-doped bismuth oxobromide nanosheets for self-activated photodynamic therapy

Low tissue penetration depth of the excited light and complicated synthetic procedures greatly hinder the clinical application of photodynamic therapy (PDT). Here we present a facile and mass production route to fabricate Yb3+/Tm3+ co-doped BiOBr nanosheets. In contrast to the complicated combination of photosensitizers (PSs) with up-conversion nanoparticles (UCNPs), which generates a PDT effect by a fluorescence resonance energy transfer process from UCNPs to PSs upon near-infrared light excitation, this as-synthesized material can be self-activated by deep-penetrating 980 nm laser light to produce a large amount of reactive oxygen species, giving rise to a high PDT efficiency which has been proven by in vitro and in vivo therapeutic assays. Surface modification of the BiOBr:Yb,Tm nanosheets with polyethylene glycol endows the system with improved biocompatibility. Through the combination of inherent fluorescence and CT imaging properties, an imaging-monitored therapeutic system has been realized. The system overcomes the problems of low tissue penetration depth, complicated structure-induced low efficiency, and potential safety concerns. Our finding presents the first demonstration of a self-activated nanoplatform for targeted and noninvasive deep-cancer therapy.

Near-infrared light-induced imaging and targeted anti-cancer therapy based on a yolk/shell structure

To combine photodynamic therapy (PDT) and bio-imaging for improved antitumor efficacy, we design a yolk-like NaYF4:Yb,Er@MgSiO3–ZnPc–RGD mesoporous platform by encapsulating a photosensitive agent (ZnPc) and a targeted peptide, NH2-Gly-Arg-Gly-Asp-Ser (RGD), into MgSiO3 mesoporous shell coated NaYF4:Yb,Er spheres. A novel spinous MgSiO3 shell is synthesized by an in situ growth process without using any surfactant, instead of the conventional mesoporous silica shell. Upon 980 nm laser irradiation, the emitted red light matches well with the absorbance of ZnPc, which generates reactive oxygen species (ROS) to kill cancer cells, and the retained green light allows for real-time monitoring of the therapeutic process. The in vitro and in vivo results indicate that the platform shows excellent anti-cancer therapeutic efficacy under NIR laser irradiation due to the specialised intracellular transition pattern, avoiding premature leakout of ZnPc, and targeted accumulation in the cancer cell sites. Thus, we envision that our proposed platform should have great potential for PDT-induced tumor therapy and for monitoring biochemical changes taking place in live tumor cells.