The immediate release of chemotherapeutics at the target site, along with no premature release in circulation is always challenging. The purpose of this study was to develop a stimuli responsive drug delivery system, composed of lipid supported mesoporous silica nanoparticles (MSNPs) for triggered drug release at the target site and simultaneously avoiding the premature release. MSNPs with a higher drug loading capacity and very slow release were designed so as to enhance release by FDA approved US-irradiation. Doxorubicin, as a model drug, and perfluoropentane (PFP) as a US responsive material, were entrapped in the porous structure of MSNPs. Lipid coating enhanced the cellular uptake and in addition provided a gatekeeping effect at the pore opening to reduce premature release. The mechanical and thermal effects of US induced the conversion of liquid PFP to a gaseous form that was able to rupture the lipid layer, resulting in triggered drug release. The prolonged stability profile and non-toxic behavior made them suitable candidate for the delivery of anticancer drugs. This smart system, with the abilities of better cellular uptake and higher cytotoxic effects on US-irradiation, would be a good addition to the applied side of chemotherapeutic advanced drug delivery systems.

Cancer is a global health burden and is one of the leading causes of death. Photodynamic therapy (PDT) is considered an alternative approach to conventional cancer treatment. PDT utilizes a light-sensitive compound, photosensitizers (PSs), light irradiation, and molecular oxygen (O₂). This generates cytotoxic reactive oxygen species (ROS), which can trigger necrosis and/ or apoptosis, leading to cancer cell death in the intended tissues. Classical photosensitizers impose limitations that hinder their clinical applications, such as long-term skin photosensitivity, hydrophobic nature, nonspecific targeting, and toxic cumulative effects. Thus, nanotechnology emerged as an unorthodox solution for improving the hydrophilicity and targeting efficiency of PSs. Among nanocarriers, mesoporous silica nanoparticles (MSNs) have gained increasing attention due to their high surface area, defined pore size and structure, ease of surface modification, stable aqueous dispersions, good biocompatibility, and optical transparency, which are vital for PDT. The advancement of integrated MSNs/PDT has led to an inspiring multimodal nanosystem for effectively treating malignancies. This review gives an overview of the main components and mechanisms of the PDT process, the effect of PDT on tumor cells, and the most recent studies that reported the benefits of incorporating PSs into silica nanoparticles and integration with PDT against different cancer cells.

Since the available treatments are not highly effective to combat cancer, therefore, the alternative strategies are unavoidable. Photodynamic therapy (PDT) is one of the emerging approaches which is target specific and minimally invasive. This study explores the successful development of Poly (D,L-lactide-co-glycolide) (PLGA) coated mesoporous silica nanoparticles (MSNs) and their augmented effects achieved by integrating curcumin (Cur) and cetyltrimethylammonium bromide (CTAB) in the polymeric layer and silica's pores, respectively. The synthesized nanocarriers (Cur-PLGA-cMSNs) have shown preferential targeting to the cellular organelles facilitated by CTAB's and Cur's affinity to mitochondria. CTAB and Cur-based PDT induced oxidative stress and generation of reactive oxygen species (ROS), resulting in dysfunctional mitochondria and triggered apoptotic pathways. PLGA coating has produced multifunctional effects, including; gatekeeping effects at pore openings, providing an extra loading site, enhancing the hemocompatibility of MSNs, and masking the free cur-related prolonged coagulation time. Cur-PLGA-cMSNs, as a multifaceted and combative approach with synergistic effects demonstrate promising potential to enhance outcomes in cancer treatment.

This study establishes a streamlined, scalable, and reproducible workflow for the sustainable and computationally guided development of nanostructured lipid carriers (NLCs) by integrating Quality by Design and molecular simulations with sustainable approaches in formulating plant-based NLCs loaded with curcumin (CUR) as a model natural molecule. Our approach aims to accelerate the screening, optimization, and development processes of nanoformulations while maintaining drug loading and stability and adhering to green chemistry principles. A combined-mixture process and a 3² Factorial/RSM experimental design were used. NLCs were prepared using high-shear hot homogenization at 12,000 RPM for 10 min. Following characterization, NLCs were optimized and evaluated. Molecular dynamics simulations were conducted using GROMACS to study the interaction between CUR and NLCs. The optimized CUR-NLCs had a particle size (80.28 - 87.31 nm), PDI (0.239 - 0.276), and Zeta potential (-11.63 to -14.67 mV), with an encapsulation efficiency (53 - 63 %). The optimized CUR-NLCs demonstrated desirable properties while using plant-based materials and sustainable methods. Employing molecular simulations provided insights into the assembly of NLCs and CUR interactions with their components. The proof-of-concept successfully bridged process optimization with advanced computational pharmaceutics, ensuring that digital transformation and sustainability are at the core of future nanoformulation research and industrial adoption.

The potential of levosulpiride-loaded nanostructured lipid carriers (LSP-NLCs) for enhanced antidepressant and anxiolytic effects was evaluated in the current study. A forced swim test (FST) and tail suspension test (TST) were carried out to determine the antidepressant effect whereas anxiolytic activity was investigated using light–dark box and open field tests. Behavioral changes were evaluated in lipopolysaccharide-induced depressed animals. The access of LSP to the brain to produce therapeutic effects was estimated qualitatively by using fluorescently labeled LSP-NLCs. The distribution of LSP-NLCs was analyzed using ex vivo imaging of major organs after oral and intraperitoneal administration. Acute toxicity studies were carried out to assess the safety of LSP-NLCs in vivo. An improved antidepressant effect of LSP-NLCs on LPS-induced depression showed an increase in swimming time (237 ± 51 s) and struggling time (226 ± 15 s) with a reduction in floating (123 ± 51 s) and immobility time (134 ± 15 s) in FST and TST. The anxiolytic activity in the light–dark box and open field tests exhibited superiority over LSP dispersion. Near-infrared images of fluorescently labeled LSP-NLCs demonstrated the presence of coumarin dye in the brain after 1 h of administration. An acute toxicity study revealed no significant changes in organ-to-body weight ratio, serum biochemistry or tissue histology of major organs. It can be concluded that nanostructured lipid carriers can efficiently deliver LSP to the brain for improved therapeutic efficacy.

Background: Photodynamic therapy (PDT) has evolved as a reliable therapeutic modality for cancer. However, the broad application of the technique is still limited because of poor bioavailability and the non-selective distribution of photosensitizers within host tissues. Herein, zein, a natural corn protein, was functionalized with glycyrrhetinic acid (GA) and polyethylene glycol (Z-PEG-GA) as a targeting platform for liver cancer cells. Parietin, as novel photosensitizer, was successfully encapsulated into zein via nanoprecipitation and used for the therapy of hepatocellular carcinoma. Methods: The in vitro phototoxicity of Z-PEG-GA nanoparticles and their non-functionalized control (Z-PEG) were assessed against hepatocellular carcinoma (HepG2 cells) and the In vivo biodistribution was determined in an adult male CD-1 Swiss albino mice model. Results: The formulated Z-PEG and Z-PEG-GA showed spherical shapes with average sizes of 82.8 and 94.7 nm for unloaded nanoparticles, respectively, and 109.7 and 111.5 nm for loaded nanoparticles carrying more than 70% of parietin, and Quantum yield measurements show that parietin’s photodynamic potential is conserved. Moreover, parietin-loaded Z-PEG-GA exhibited three-fold higher toxicity against liver cancer cells than its non-functionalized control and attained more than an eleven-fold enhancement in the generated intracellular reactive oxygen species (ROS) at a 9 J/cm² radiant exposure. The generated intracellular ROS led to mitochondrial disruption and the release of cytochrome c. In vivo biodistribution studies revealed that fluorescence signals of Z-PEG-GA can persist in the excised animal liver for up to 24 h post-administration. Conclusions: Consequently, tailored zein can hold great potential for delivering several hydrophobic photosensitizers in anticancer PDT.