Surface engineered multifunctional nano-systems for localised drug delivery against thyroid cancer: A review of current practices.

Thyroid cancer, the most prevalent cancer of the endocrine system and cervical region, has experienced a significant increase in incidence over recent decades. Nanomedicine has fundamentally revolutionized cancer treatment, particularly through the development of multifunctional nano-therapeutics. The progress in this field has been facilitated by the distinctive properties of nanomaterials, such as their capacity to perform several functions, be modified, and offer various detection methods. These features allow for non-invasive and practical diagnostic techniques through versatile imaging. Surface engineering plays a pivotal role in the design of multifunctional nano-systems for localized drug delivery against thyroid cancer. Nano-systems can be customized via surface modification techniques, such as functionalization with targeting ligands and inclusion of therapeutic drugs. This customization allows the nano-systems to specifically target cancer cells while reducing the impact on non-target cells. As a result, bovine serum albumin-coated nanostructures have emerged as powerful diagnostic and targeting nanosystems for thyroid cancer. This targeted strategy enhances the effectiveness of cancer treatment while reducing overall body toxicity. This comprehensive review aims to provide an extensive overview of the latest advancements in surface-engineered nanoparticle-based approaches for both diagnosing and treating thyroid cancer. It highlights the promising research endeavors aimed at creating novel and effective multifunctional nanomedicine for localized delivery to thyroid cancer sites. The review examines different nanomedicines that have been developed for cancer treatment and diagnosis. It also analyzes the current trends, future possibilities, and obstacles in this rapidly advancing sector. By synthesizing the current state of knowledge on surface-engineered multifunctional nano-systems, this review contributes to a better understanding of their potential applications in thyroid cancer treatment and paves the way for future research directions in this promising field of nanomedicine.

Mitochondrial-targeted and ROS-responsive nanocarrier via nose-to-brain pathway for ischemic stroke treatment.

Oxidative stress injury and mitochondrial dysfunction are major obstacles to neurological functional recovery after ischemic stroke. The development of new approaches to simultaneously diminish oxidative stress and resist mitochondrial dysfunction is urgently needed. Inspired by the overproduced reactive oxygen species (ROS) at ischemic neuron mitochondria, multifunctional nanoparticles with ROS-responsiveness and mitochondrial-targeted (SPNPs) were engineered, achieving specific targeting delivery and controllable drug release at ischemic penumbra. Due to the nose-to-brain pathway, SPNPs which were encapsulated in a thermo-sensitive gel by intranasal administration were directly delivered to the ischemic penumbra bypassing the blood‒brain barrier (BBB) and enhancing delivery efficiency. The potential of SPNPs for ischemic stroke treatment was systematically evaluated in vitro and in rat models of middle cerebral artery occlusion (MCAO). Results demonstrated the mitochondrial-targeted and protective effects of SPNPs on H2O2-induced oxidative damage in SH-SY5Y cells. In vivo distribution analyzed by fluorescence imaging proved the rapid and enhanced active targeting of SPNPs to the ischemic area in MCAO rats. SPNPs by intranasal administration exhibited superior therapeutic efficacy by alleviating oxidative stress, diminishing inflammation, repairing mitochondrial function, and decreasing apoptosis. This strategy provided a multifunctional delivery system for the effective treatment of ischemic injury, which also implies a potential application prospect for other central nervous diseases.

A Multifunctional Nanocarrier System for Highly Efficient and Targeted Delivery of Ketamine to NMDAR Sites for Improved Treatment of Depression.

Ketamine (KA), commonly used as an anesthetic, is now widely studied as an antidepressant for the treatment of depression. However, due to its side effects, such as addiction and cognitive impairment, the dosage and frequency of (S)-ketamine approved by the FDA for the treatment of refractory depression is very low, which limits its efficacy. Here, a new multifunctional nanocarrier system (AC-RM@HA-MS) with specific targeting capabilities is developed to improve the efficacy of KA treatment. KA-loaded NPs (AC-RM@HA-MS-KA) are constructed with a multilayer core-shell structure. KA-loaded mesoporous silica NPs are prepared, conjugated with hyaluronic acid (HA) as pore gatekeepers, and sheathed with an RBC-membrane (RM) for camouflage. Finally, the surface is tagged with bifunctional peptides (Ang-2-Con-G, AC) to achieve specific targeting. One peptide (Ang-2) is acted as a guide to facilitate the crossing of the blood-brain barrier (BBB), while the other (Con-G) is functioned as a ligand for the targeted delivery of KA to the N-methyl-D-aspartate receptor sites. Animal experiments reveal that AC-RM@HA-MS-KA NPs effectively cross the BBB and directionally accumulate in the curing areas, thereby alleviating the depressive symptoms and improving the cognitive functions of depressed mice. After treatment, the depressed mice almost completely return to normal without obvious symptoms of addiction.

Mitochondrial-targeted and ROS-responsive nanocarrier via nose-to-brain pathway for ischemic stroke treatment

Oxidative stress injury and mitochondrial dysfunction are major obstacles to neurological functional recovery after ischemic stroke. The development of new approaches to simultaneously diminish oxidative stress and resist mitochondrial dysfunction is urgently needed. Inspired by the overproduced reactive oxygen species (ROS) at ischemic neuron mitochondria, multifunctional nanoparticles with ROS-responsiveness and mitochondrial-targeted (SPNPs) were engineered, achieving specific targeting delivery and controllable drug release at ischemic penumbra. Due to the nose-to-brain pathway, SPNPs which were encapsulated in a thermo-sensitive gel by intranasal administration were directly delivered to the ischemic penumbra bypassing the blood‒brain barrier (BBB) and enhancing delivery efficiency. The potential of SPNPs for ischemic stroke treatment was systematically evaluated in vitro and in rat models of middle cerebral artery occlusion (MCAO). Results demonstrated the mitochondrial-targeted and protective effects of SPNPs on H2O2-induced oxidative damage in SH-SY5Y cells. In vivo distribution analyzed by fluorescence imaging proved the rapid and enhanced active targeting of SPNPs to the ischemic area in MCAO rats. SPNPs by intranasal administration exhibited superior therapeutic efficacy by alleviating oxidative stress, diminishing inflammation, repairing mitochondrial function, and decreasing apoptosis. This strategy provided a multifunctional delivery system for the effective treatment of ischemic injury, which also implies a potential application prospect for other central nervous diseases.

Multifunctional nanocarriers for delivering siRNA and miRNA in glioblastoma therapy: advances in nanobiotechnology-based cancer therapy.

Glioblastoma multiforme (GBM) is one of the most lethal cancer due to poor diagnosis and rapid resistance developed towards the drug. Genes associated to cancer-related overexpression of proteins, enzymes, and receptors can be suppressed using an RNA silencing technique. This assists in obtaining tumour targetability, resulting in less harm caused to the surrounding healthy cells. RNA interference (RNAi) has scientific basis for providing potential therapeutic applications in improving GBM treatment. However, the therapeutic application of RNAi is challenging due to its poor permeability across blood-brain barrier (BBB). Nanobiotechnology has evolved the use of nanocarriers such as liposomes, polymeric nanoparticles, gold nanoparticles, dendrimers, quantum dots and other nanostructures in encasing the RNAi entities like siRNA and miRNA. The review highlights the role of these carriers in encasing siRNA and miRNA and promising therapy in delivering them to the glioma cells.

Mn2+ /Fe3+ /Co2+ and Tetrasulfide Bond Co-Incorporated Dendritic Mesoporous Organosilica as Multifunctional Nanocarriers: One-Step Synthesis and Applications for Cancer Therapy.

Enriching the application of multifunctional dendritic mesoporous organosilica (DMOS) is still challenging in anti-cancer research. Herein, manganese ions, iron ions, or cobalt ions and tetrasulfide bonds are co-incorporated into the framework of DMOS to yield multifunctional nanoparticles denoted as Mn-DMOS, Fe-DMOS, or Co-DMOS by directly doping metal ions during the synthetic process. Due to co-incorporation of metal ions and tetrasulfide bonds, these designed nanocarriers have more functions rather than only for cargo delivery. As proof of concept, the nanocomposite is established based on Mn-DMOS as an efficient nanocarrier for indocyanine green (ICG) delivery and modification with polyethylene glycol. In the tumor microenvironment, the generated hydrogen sulfide (H2 S) arising from the reaction between tetrasulfide bond and over-expressed glutathione (GSH) causes mitochondrial injury to reduce cellular respiration. The released Mn2+ from the rapidly decomposed nanocomposite catalyzes the endogenous hydrogen peroxide to produce oxygen (O2 ). The photothermal effect from the released ICG initiated by the near-infrared light induces cancer cells apoptosis and simultaneously enhances the content of blood O2 at tumor sites. Therefore, due to the GSH depletion and trimodal O2 compensation, the photodynamic therapy efficiency of ICG has significantly improved. In brief, these designed nanocarriers will play advanced roles in cancer therapy.

Current Advances in Multifunctional Nanocarriers Based on Marine Polysaccharides for Colon Delivery of Food Polyphenols.

Inflammatory bowel disease (IBD) has been considered as a chronic disease that is difficult to cure and needs lifelong treatment. Marine polysaccharides with good biocompatibility and biodegradability, mucoadhesion, sensitivity to external stimuli, and targeting ability can be used as wall materials for oral colon-targeted delivery of polyphenols in nutrition intervention of IBD. This manuscript reviewed the latest progress in the design, preparation, and characterization of marine polysaccharides-derived multifunctional nanocarriers for polyphenol colon delivery. Chitosan, sodium alginate, chondroitin sulfate, and hyaluronic acid were discussed in the preparation of polyphenol delivery systems. The design strategy, synthesis methods, and structure characterization of multifunctional polyphenol carriers including stimuli-responsive nanocarriers, mucoadhesive and mucus-penetrating nanocarriers, colon targeted nanocarriers, and bioactive compounds codelivery nanocarriers were reviewed in the alleviation of IBD. The research perspectives in the preparation and characterization of delivery carriers using marine polysaccharide as materials were proposed for their potential application in food bioactive components.

A biocompatible nanoplatform formed by MgAl-layered double hydroxide modified Mn3O4/N-graphene quantum dot conjugated-polyaniline for pH-triggered release of doxorubicin.

In this work, for the first time, a novel pH-sensitive biocompatible multifunctional nanocarrier was fabricated by the combination of MgAl-layered double hydroxide, Mn3O4 nanoparticles, N-graphene quantum dot and polyaniline (PANI/N-GQD/MO/LDH) for doxorubicin (DOX) delivery in breast cancer cells. Electrochemical techniques, including cyclic voltammetry (CV) and differential pulse voltammetry (DPV), were employed for proving the surface modification process. The integration of polyaniline on the surface of the nanocarrier provides ultrahigh DOX encapsulation up to 90% and possesses a slow-release behavior (4% after 72 h) under normal physiological conditions. However, releasing ~80% of the drug in a low-pH environment as a model of the extracellular tumor environment happened, presenting a pH-triggered release. The cell viability using MTT assay reveals that the DOX/PANI/N-GQD/MO/LDH had no apparent adverse effect on the viability of human L929 normal cells. Furthermore, a significant inhibition ratio against human breast cancer cell lines (MCF-7) was observed when the cells were treated with the DOX-loaded PANI/N-GQD/MO/LDH nanocarrier, suggesting that this nanocarrier could increase the therapeutic efficacy of DOX. The hemolysis rates (HRs) of human fresh blood, coagulation prothrombin time (PT), activated partial thromboplastin time (APTT), and complement activation (C3 and C4 levels) revealed the excellent blood compatibility of the nanocarrier. Thus, the nano-vehicle designed in this study could be used as a novel multifunctional and synergistic, pH-triggered platform for delivering various anti-cancer drugs and other biomedical applications.

Highlights in Mesoporous Silica Nanoparticles as a Multifunctional Controlled Drug Delivery Nanoplatform for Infectious Diseases Treatment.

Infectious diseases are a major global concern being responsible for high morbidity and mortality mainly due to the development and enhancement of multidrug-resistant microorganisms exposing the fragility of medicines and vaccines commonly used to these treatments. Taking into account the scarcity of effective formulation to treat infectious diseases, nanotechnology offers a vast possibility of ground-breaking platforms to design new treatment through smart nanostructures for drug delivery purposes. Among the available nanosystems, mesoporous silica nanoparticles (MSNs) stand out due their multifunctionality, biocompatibility and tunable properties make them emerging and actual nanocarriers for specific and controlled drug release. Considering the high demand for diseases prevention and treatment, this review exploits the MSNs fabrication and their behavior in biological media besides highlighting the most of strategies to explore the wide MSNs functionality as engineered, smart and effective controlled drug release nanovehicles for infectious diseases treatment. Graphical Abstract Schematic representation of multifunctional MSNs-based nanoplatforms for infectious diseases treatment.

Nanoparticles-assisted delivery of antiviral-siRNA as inhalable treatment for human respiratory viruses: A candidate approach against SARS-COV-2.

The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has challenged healthcare structures across the globe. Although a few therapies are approved by FDA, the search for better treatment options is continuously on rise. Clinical management includes infection prevention and supportive care such as supplemental oxygen and mechanical ventilatory support. Given the urgent nature of the pandemic and the number of companies and researchers developing COVID-19 related therapies, FDA has created an emergency program to move potential treatments with already approved drugs to patients as quickly as possible in parallel to the development of new drugs that must first pass the clinical trials. In this manuscript, we have reviewed the available literature on the use of sequence-specific degradation of viral genome using short-interfering RNA (siRNA) suggesting it as a possible treatment against SARS-CoV-2. Delivery of siRNA can be promoted by the use of FDA approved lipids, polymers or lipid-polymer hybrids. These nanoparticulate systems can be engineered to exhibit increased targetability and formulated as inhalable aerosols.

Creatine based polymer for codelivery of bioengineered MicroRNA and chemodrugs against breast cancer lung metastasis.

Metastasis is the major cause for breast cancer related mortality. The combination of miRNA-based therapy and chemotherapy represents a promising approach against breast cancer lung metastasis. The goal of this study is to develop an improved therapy that co-delivers a novel bioengineered miRNA prodrug (tRNA-mir-34a) and doxorubicin (DOX) via a multifunctional nanomicellar carrier that is based on a conjugate of amphiphilic copolymer POEG-VBC backbone with creatine, a naturally occurring cationic molecule. Co-delivery of DOX leads to more effective processing of tRNA-mir-34a into mature miR-34a and down-regulation of target genes. DOX + tRNA-mir-34a/POEG-PCre exhibits potent synergistic anti-tumor and anti-metastasis activity in vitro and in vivo. Interestingly, the enhanced immune response contributes to the overall antitumor efficacy. POEG-PCre may represent a safe and effective delivery system for an optimal chemo-gene combination therapy.

Co-delivery strategies to overcome multidrug resistance in ovarian cancer.

Cancer is one of the leading causes of death and equally strikes both genders. Among women, ovarian cancer is responsible for many deaths as it remains symptomless in the earlier stages and generally diagnosed in third stage. At this point it becomes difficult to carry out de-bulking surgery and treatment with different chemotherapeutic drugs has shown resistance, a phenomenon known as multidrug resistance (MDR). Different treatment choices are available for ovarian cancer; however, this article only focuses on various co-delivery strategies, where two different agents are encapsulated in a single carrier and act via different pathways to overcome cancer cell resistance. Ovarian cancer develops MDR via different pathways but majorly involving pump and the non-pump mechanisms in most cases. To overcome MDR it is imperative to strike malignant cells from various directions. Nanocarriers are known to strike the pump mechanism by avoiding the drug efflux pump located on cellular membrane. The efflux pump can also be blocked by blocking activity of ATP binding cassette (ABC) membrane transporters. To stop the non-pump mechanism one can use chemosensitizers, genes, apoptotic factor and others. Treatment of cancer cells could even more effective if the drug is combined with co-agents in a single carrier with targeting moiety. These co-agents along with nanocarriers, allow the drug to accumulate in high enough concentrations in ovarian cancer cells to kill them without affecting normal cells.

Cyclodextrin-Modified inorganic materials for the construction of nanocarriers.

Inorganic nanoparticles, such as gold, silver, quantum dots and magnetic nanoparticles, offer a promising way to develop multifunctional nanoparticles for biomedical applications. Such nanoparticles have the potential to combine in a single, stable construct various functionalities, simultaneously providing imaging abilities, thermal therapies and the ability to deliver drugs in a targeted fashion. An approach for providing drug loading abilities to these inorganic nanoparticles consists in the modification of their surface with a coating of cyclodextrins, and thereby endowing the nanoparticles with the potential of functioning as drug nanocarriers. This review presents the advances carried out in the preparation of cyclodextrin-contained gold, silver, quantum dot and magnetic nanoparticles as well as their applications as drug nanocarriers. The nanoparticle surface can be modified incorporating cyclodextrin moieties, (i) in situ during the synthesis of the nanoparticles, either using the cyclodextrin as reducing agent or as stabilizer; or (ii) in a post-synthetic stage. The cyclodextrin coating contributes to provide biocompatibility to the nanoparticles and to reduce their cytotoxicity. Cyclodextrin-modified nanoparticles display a multivalent presentation of quasi-hydrophobic cavities that enables, not only drug loading in a non-covalent manner, but also the non-covalent assembly of targeting motifs and optical probes. This paper also provides an overview of some of the reported applications including the in vitro studies and, to a lesser extent, in vivo studies on the drug-loaded nanoparticles behavior.

Protein-Based Multifunctional Nanocarriers for Imaging, Photothermal Therapy, and Anticancer Drug Delivery.

We report a simple approach for fabricating plasmonic and magneto-luminescent multifunctional nanocarriers (MFNCs) by assembling gold nanorods, iron oxide nanoparticles, and gold nanoclusters within BSA nanoparticles. The MFNCs showed self-tracking capability through single- and two-photon imaging, and the potential for magnetic targeting in vitro. Appreciable T2-relaxivity exhibited by the MFNCs indicated favorable conditions for magnetic resonance imaging. In addition to successful plasmonic-photothermal therapy of cancer cells (HeLa) in vitro, the MFNCs demonstrated efficient loading and delivery of doxorubicin to HeLa cells leading to significant cell death. The present MFNCs with their multimodal imaging and therapeutic capabilities could be eminent candidates for cancer theranostics.

Surface Modified Multifunctional and Stimuli Responsive Nanoparticles for Drug Targeting: Current Status and Uses.

Nanocarriers, due to their unique features, are of increased interest among researchers working with pharmaceutical formulations. Polymeric nanoparticles and nanocapsules, involving non-toxic biodegradable polymers, liposomes, solid lipid nanoparticles, and inorganic-organic nanomaterials, are among the most used carriers for drugs for a broad spectrum of targeted diseases. In fact, oral, injectable, transdermal-dermal and ocular formulations mainly consist of the aforementioned nanomaterials demonstrating promising characteristics such as long circulation, specific targeting, high drug loading capacity, enhanced intracellular penetration, and so on. Over the last decade, huge advances in the development of novel, safer and less toxic nanocarriers with amended properties have been made. In addition, multifunctional nanocarriers combining chemical substances, vitamins and peptides via coupling chemistry, inorganic particles coated by biocompatible materials seem to play a key role considering that functionalization can enhance characteristics such as biocompatibility, targetability, environmental friendliness, and intracellular penetration while also have limited side effects. This review aims to summarize the "state of the art" of drug delivery carriers in nanosize, paying attention to their surface functionalization with ligands and other small or polymeric compounds so as to upgrade active and passive targeting, different release patterns as well as cell targeting and stimuli responsibility. Lastly, future aspects and potential uses of nanoparticulated drug systems are outlined.

Engineered multifunctional nanomaterials for multimodal imaging of retinoblastoma cells in vitro.

Multifunctional nanoparticles are next generation materials that can be simultaneously used for imaging, diagnosis, and delivery of drugs. However, materials intended for cancer diagnosis need to be investigated for its cell uptake, toxicity, and effectiveness. In the current work, we have synthesized fluorescent iron oxide nanoparticles and evaluated its efficacy against retinoblastoma cell imaging. The iron oxide nanoparticles were synthesized and stabilized using oleic acid. Sulforhodamine B was adsorbed onto albumin over the oleic acid-capped iron oxide nanoparticles. Our results demonstrated good cell uptake in a time-dependent manner and nanoparticles were found to localize in the cytosol. Further, the nanoparticles exhibited excellent negative contrast in magnetic resonance imaging (MRI) experiments and with no cytoxicity (5-100 µg/mL iron oxide nanoparticles) to both normal as well as cancer cells demonstrating its biocompatibility. Thus, this novel material integrates the ability to image tissues with high sensitivity by MRI and specifically visualize Y79 retinoblastoma cells by fluorescence imaging with no toxicity.

Recent advances in delivery of drug-nucleic acid combinations for cancer treatment.

Cancer treatment that uses a combination of approaches with the ability to affect multiple disease pathways has been proven highly effective in the treatment of many cancers. Combination therapy can include multiple chemotherapeutics or combinations of chemotherapeutics with other treatment modalities like surgery or radiation. However, despite the widespread clinical use of combination therapies, relatively little attention has been given to the potential of modern nanocarrier delivery methods, like liposomes, micelles, and nanoparticles, to enhance the efficacy of combination treatments. This lack of knowledge is particularly notable in the limited success of vectors for the delivery of combinations of nucleic acids with traditional small molecule drugs. The delivery of drug-nucleic acid combinations is particularly challenging due to differences in the physicochemical properties of the two types of agents. This review discusses recent advances in the development of delivery methods using combinations of small molecule drugs and nucleic acid therapeutics to treat cancer. This review primarily focuses on the rationale used for selecting appropriate drug-nucleic acid combinations as well as progress in the development of nanocarriers suitable for simultaneous delivery of drug-nucleic acid combinations.