Strategy For Targeted Delivery Research Articles

Blood–Brain Barrier-Targeting Nanoparticles: Biomaterial Properties and Biomedical Applications in Translational Neuroscience

Overcoming the blood–brain barrier (BBB) remains a significant hurdle in effective drug delivery to the brain. While the BBB serves as a crucial protective barrier, it poses challenges in delivering therapeutic agents to their intended targets within the brain parenchyma. To enhance drug delivery for the treatment of neurological diseases, several delivery technologies to circumvent the BBB have been developed in the last few years. Among them, nanoparticles (NPs) are one of the most versatile and promising tools. Here, we summarize the characteristics of NPs that facilitate BBB penetration, including their size, shape, chemical composition, surface charge, and importantly, their conjugation with various biological or synthetic molecules such as glucose, transferrin, insulin, polyethylene glycol, peptides, and aptamers. Additionally, we discuss the coating of NPs with surfactants. A comprehensive overview of the common in vitro and in vivo models of the BBB for NP penetration studies is also provided. The discussion extends to discussing BBB impairment under pathological conditions and leveraging BBB alterations under pathological conditions to enhance drug delivery. Emphasizing the need for future studies to uncover the inherent therapeutic properties of NPs, the review advocates for their role beyond delivery systems and calls for efforts translating NPs to the clinic as therapeutics. Overall, NPs stand out as a highly promising therapeutic strategy for precise BBB targeting and drug delivery in neurological disorders.

Hyaluronic acid modified extracellular vesicles targeting hepatic stellate cells to attenuate hepatic fibrosis

RationaleTransforming growth factor-beta1 (TGF-β1) plays a pivotal role in promoting hepatic fibrosis, pirfenidone (PFD) could inhibit TGF-β1 signaling pathway to alleviate hepatic stellate cells (HSC) activation mediated hepatic fibrosis. The targeting delivery strategy of PFD to hepatic stellate cells is a challenge. Extracellular vesicles (EVs), cell-derived membranous particles are intraluminal nano-vesicles that play a vital role in intercellular communication, they also be considered as an ideal nano-carrier. MethodsIn this study, we developed a target strategy to deliver PFD to HSC with CD44 over-expression by EVs, hyaluronic acid (HA) modified DSPE-PEG2000 endows the active targeting ability of activated HSCs to PFD-loaded EVs. ResultsIn both rat hepatic stellate cell line HSC-T6 and rat hepatocyte cell line BRL, HA@EVs-PFD demonstrated the capacity to down-regulate the expression of collagen-synthesis-related proteins and showed superior inhibition efficacy of HSC-T6 activation compared to free PFD. In hepatic fibrosis model, 4 weeks of HA@EVs-PFD treatment resulted in a reduction in liver collagen fibers, significant improvement in hepatic cell morphology, and amelioration of hepatic fibrosis. ConclusionsHA@EVs-PFD, as a drug delivery system that effectively targets and inhibits activated HSCs to treat hepatic fibrosis, holds promise as a potential therapeutic agent against hepatic fibrosis.

CAPN2-responsive mesoporous silica nanoparticles: A promising nanocarrier for targeted therapy of pancreatic cancer

Pancreatic adenocarcinoma (PDAC) is highly resistant to conventional chemotherapeutic interventions, resulting in exceptionally low survival rates. The limited efficacy can in part be attributed to dose limitations and treatment cessation urged by toxicity of currently used chemotherapy. The advent of targeted delivery strategies has kindled hope for circumventing off-target toxicity. We have previously reported a PDAC-specific mesoporous silica nanoparticle (MSN) containing a protease linker responsive to ADAM9, a PDAC-enriched extracellularly deposited protease. Upon loading with paclitaxel these ADAM9-MSNs reduced side effects both in vitro and in vivo, however, disappointing antitumor efficacy was observed in vivo. Here, we propose that an efficient uptake of MSNs by tumor cells might underlie the lack of antitumor efficacy of MSNs functionalized with linker responsive to extracellular proteases. Harnessing this premise to improve antitumor efficacy, we performed an in silico analysis to identify PDAC-enriched intracellular proteases. We report the identification of BACE2, CAPN2 and DPP3 as PDAC enriched intracellular proteases, and report the synthesis of BACE2-, CAPN2- and DPP3-responsive MSNs. Extensive preclinical assessments revealed that paclitaxel-loaded CAPN2- and DPP3-MSNs exhibit high PDAC specificity in vitro as opposed to free paclitaxel. The administration of paclitaxel-loaded CAPN2- and DPP3-MSNs in vivo confirmed the reduction of leukopenia and induced no organ damage. Promisingly, in two mouse models CAPN2-MSNs reduced tumor growth at least as efficiently as free paclitaxel. Taken together, our results pose CAPN2-MSNs as a promising nanocarrier for the targeted delivery of chemotherapeutics in PDAC.

Foliar application of glycine-functionalized nanopesticides for effective prevention and control of root-knot nematodes via a targeted delivery strategy.

Root-knot nematodes (RKNs) are the highly damaging pests for various crops, and the prevalence of RKNs has posed serious threats to worldwide agricultural harvest, severely affecting global food security and ecosystem health. Traditional pesticide systems on controlling RKNs generally cause environmental hazards and phytotoxicity due to the excessive use of pesticides resulted from low utilization efficiency. And effective approaches with biosafe and efficient features are highly demanded to break away from the dilemma caused by RKNs. In this research, a nanopesticide system with root-targeted delivery function was developed to achieve effective prevention and control of RKNs. The nanocarriers (MSN-KH560-Gly) and the obtained nanopesticides (EB@MSN-KH560-Gly) were proved to be biosafe. Also, this nanopesticide system demonstrated sustained release behavior. The grafting of glycine (Gly) significantly improved the pesticide contents translocating to cucumber roots (about 304.7%). Besides, such root-targeted delivery function resulted in no root nodule in cucumber plants after the foliar application of these nanopesticides (prevention rate of 100%). In addition, the root nodule numbers of the infected cucumber plants decreased by 71.67%. Foliar application of these Gly-functionalized nanopesticides achieved effective prevention and control of RKNs due to the root-targeted delivery property inherent in this nanopesticide system, and such root-targeted delivery strategy opens a novel and efficient method to protect crops from RKN invasion and thus facilitates the development of sustainable agriculture. © 2023 Society of Chemical Industry.

Controllable Thrombolysis Using a Nanobubble-Imaging-Guided rtPA Targeted Delivery Strategy.

Objective: The objective of this work is to design and fabricate a novel multifunctional nanocarrier combining thrombus-targeted imaging and ultrasound-mediated drug delivery for the theranostics of thrombotic diseases. Impact Statement: This study develops a new technology that can accurately visualize the thrombus and deliver drugs with controllable properties to diagnose and treat thrombotic diseases. Introduction: Thrombotic diseases are a serious threat to human life and health. The diagnosis and treatment of thrombotic diseases have always been a challenge. In recent years, nanomedicine has brought new ideas and new methods for the theranostics of thrombotic diseases. However, there are also many problems need to be solved, such as biosafety and stability of nanocarriers, early diagnosis, and timely treatment of thrombotic diseases, difficulty in clinical translation. Methods: The S1P@CD-PLGA-rtPA nanobubbles (NBs) were prepared by integrating sulfur hexafluoride (SF6)-loaded poly (D, L-lactide-co-glycolide) (PLGA) NBs, cyclodextrin (CD), sphingosine-1-phosphate (S1P), and recombinant tissue plasminogen activator (rtPA). Results: S1P@CD-PLGA-rtPA NBs had rapid and excellent thrombosis targeting imaging performance based on the specific interaction of S1P-S1PR1 (sphingosine-1-phosphate receptor 1). Furthermore, S1P@CD-PLGA-rtPA NBs that specifically targeting to the thrombosis regions could also respond to external ultrasound to achieve accurate and efficient delivery of rtPA to enhance the thrombolysis effectiveness and efficiency. Conclusion: This study proposes a new idea and strategy of targeting thrombus in rats via the specific interaction of S1P-S1PR1. On this basis, the acoustic response properties of bubble carriers could be fully utilized by combining thrombus-specific targeted imaging and ultrasound-mediated drug delivery for effective thrombolysis, which is expected to be applied in targeted diagnosis and treatment of thrombotic diseases in the future.

Targeting neutrophils potentiates hitchhiking delivery of drugs and agonists for postsurgical chemo-immunotherapy

Tumor resection is usually associated with tumor recurrence due to the residual tumor cells. Improving the localized accumulation of therapeutics at the surgical sites is a promising approach for the inhibition of tumor recurrence and metastasis. Herein, we report an in situ hitchhiking strategy for postsurgical tumor therapy via targeting of therapeutics-loaded liposomes to neutrophils (NEs). Anticancer drug doxorubicin (DOX) and non-nucleotide stimulator of interferon genes (STING) agonist SR-717 are encapsulated into liposomes followed by surface modification with anti-Ly6G antibodies, which can target NEs in situ in blood stream for hitchhiking delivery to the postsurgical inflamed tumor sites. The delivered DOX can inhibit the growth of residual tumor cells and trigger the tumor immunogenic cell death (ICD) for tumor-specific immunity, while SR-717 can facilitate dendritic cell maturation and enhance antitumor immunity. Consequently, the in situ NE-hitchhiking delivery of therapeutics can efficiently suppress tumor recurrence and metastatic melanoma growth after tumor resection, which circumvents the complex ex vivo processes of separation, engineering, and refusion of leukocytes and represents a targeted delivery strategy for postsurgical cancer chemo-immunotherapy.

Folic acid grafted mixed polymeric micelles as a targeted delivery strategy for tamoxifen citrate in treatment of breast cancer

The objective of this study was to develop folic acid (FA) grafted mixed polymeric micelles loaded with Tamoxifen citrate (TMXC) to enhance its antitumor activity in breast tissues. The conjugated folic acid Pluronic 123 (FA-P123) was prepared using carbonyl diimidazole cross-linker chemistry and confirmed using FTIR and 1HNMR. TMXC-loaded P123/P84 (unconjugated) and TMXC-loaded FA-P123/P84 (conjugated) micelles were examined for encapsulation efficiency, particle size, surface charge, in vitro drug release, cytotoxic effect, and cellular uptake by a breast cancer cell line. The conjugated TMXC-loaded micelle exhibited a nanoparticle size of 35.01 ± 1.20 nm, a surface charge of—20.50 ± 0.95 mV, entrapped 87.83 ± 5.10% and released 67.58 ± 2.47% of TMXC after 36 h. The conjugated micelles exhibited a significantly higher cellular uptake of TMXC by the MCF-7 cell line and improved in vitro cytotoxicity by 2.48 folds compared to the TMXC-loaded unconjugated micelles. The results of in vivo studies indicated that TMXC-loaded FA-P123/P84 has a potential antitumor activity, as revealed by a significant reduction of tumor volume in tumor-bearing mice compared to TMXC-loaded unconjugated micelles. In conclusion, the obtained results suggested that conjugated FA-P123/P84 micelles could be an encouraging carrier for the treatment of breast cancer with TMXC.Graphical abstract

Cellulose nanocrystals-based fluorescent biocarrier binding GAPDH protein with high affinity in cancer-target doxorubicin delivery

Cellulose nanocrystals (CNCs) have shown immense promise in medical applications, especially in cancer treatment, owing to their excellent biocompatibility and potential for functional modifications. Considering the crucial role of the protein reduced glyceraldehyde-phosphate dehydrogenase (GAPDH) in cancer progression, we embarked to immobilize CNCs with GAPDH and fluorescent molecules FITC, creating FCNC-G through regioselective modifications. Furthermore, an accelerated proliferation of cancer cells was observed in the presence of FCNC-G. To evaluate the therapeutic potential of FCNC-G, we loaded it with doxorubicin (DOX) to create FCNC-G-D and tested its effect on Hepg2. We observed a significant inhibition of Hepg2 cells exposed to low concentrations of FCNC-G-D. Additionally, mitochondrial dysfunction was detected in Hepg2 and Cal27 cells, treated with FCNC-G-D, but not in A375 cells, further highlighting its selective impact on cancer cells. Given the limitations of DOX in clinical applications, our findings establish a strong foundation for further research on the potential of CNCs grafted with GAPDH as a novel cancer-targeted biocarrier with high affinity. The combination of CNCs unique properties with targeted delivery strategies holds tremendous promise for the development of more effective and safer cancer therapies.

EDITORIAL

It is with immense pleasure and excitement that I extend my warmest greetings to you as we embark on a new journey with the latest issue of the International Journal of Pharmacy and Integrated Health Sciences (IJPIHS). This edition holds special significance as it focuses on the critical fields of Pharmaceutical Sciences, Clinical Pharmacy, and Drug Delivery Systems, showcasing their profound impact on healthcare applications.
 Pharmaceutical Sciences, as a multidisciplinary field, plays a pivotal role in advancing medicine and improving patient outcomes. The relentless pursuit of knowledge in this domain has led to transformative breakthroughs in drug discovery, development, and delivery, positively influencing global healthcare. In this issue, we present a diverse array of research articles, reviews, and perspectives that highlight cutting-edge advancements in pharmaceutical sciences. The journey from the laboratory to the clinic is a long and intricate one, requiring unwavering dedication and collaborative efforts from researchers, pharmacists, clinicians, and regulatory agencies. The rich tapestry of contributions in this issue is a testament to the dedication and hard work of the scientific community. The valuable insights and experiences shared by clinical pharmacy practitioners in this issue underscore the indispensable role they play in promoting safe, effective, and personalized pharmacotherapy. From nanotechnology-based carriers to targeted delivery strategies, advancements in drug delivery have redefined the possibilities of treatment modalities, enhanced therapeutic efficiency and minimized adverse effects.
 The tireless efforts of researchers in Pharmaceutical Sciences have paved the way for novel drug candidates and therapeutic interventions. Moreover, the close collaboration between researchers and clinical pharmacists ensures that these discoveries are translated into real-world clinical practice, benefiting patients across the globe. As we explore the myriad aspects of Pharmaceutical Sciences, Clinical Pharmacy, and Drug Delivery Systems in this issue, it is essential to reflect on the challenges that lie ahead. From addressing drug resistance and medication errors to ensuring equitable access to cutting-edge treatments, our collective responsibility is to surmount these hurdles and strive for the betterment of healthcare worldwide.
 As Editor in Chief of IJPIHS, I extend my heartfelt gratitude to all the authors, reviewers, and editorial team members for their unwavering commitment to maintaining the highest standards of scientific integrity. Your dedication to staying informed and sharing knowledge is the driving force behind our pursuit of excellence.
 In conclusion, I encourage all readers to immerse themselves in the enriching content of this issue, fostering curiosity and inspiring new ideas in the fields of Pharmaceutical Sciences and Integrated Health Sciences. Thank you for being part of this remarkable journey.

The new frontier of drug delivery through nanotechnology

Nanomedicine is a promising platform for drug delivery systems, offering enhanced therapeutic outcomes and reduced side effects. Nanomicelles are a class of nanoparticles that have shown great potential in delivering a wide range of therapeutics, including small molecules, proteins, and nucleic acids, to treat varied diseases and investigations. This review summarises the current state of the art in nanomedicine and its potential applications in drug delivery system. The use of Nanomicelles in topical medication delivery systems can help minimized side effects and improve patient compliance due to their improved stability and prolonged drug release capabilities. The development of stimuli-responsive micelles that can release drugs at specific conditions within the tumour microenvironment and targeted delivery strategies to enhance specificity and efficiency of gene therapy has shown promising results in terms of improved therapeutic efficacy and therapeutic efficiency. However, the presence of multidrug resistance pumps in brain cells can pose challenges in overcoming MDR mechanisms for certain drugs. These innovative approaches hold promise for enhancing the effectiveness of cancer chemotherapy in the brain and improving the prognosis for patients with brain tumours.

Cargo-Dependent Targeted Cellular Uptake Using Quaternized Starch as a Carrier

The tailored design of drug delivery systems for specific therapeutic agents is a prevailing approach in the field. In this paper, we present a study that highlights the potential of our modified starch, Q-starch, as a universal and adaptable drug delivery carrier for diverse therapeutic agents. We investigate the ability of Q-starch/cargo complexes to target different organelles within the cellular landscape, based on the specific activation sites of therapeutic agents. Plasmid DNA (pDNA), small interfering RNA (siRNA), and phosphatidylinositol (3,4,5)-trisphosphate (PIP3) were chosen as representative therapeutic molecules, acting in the nucleus, cytoplasm, and membrane, respectively. By carrying out comprehensive characterizations, employing dynamic light scattering (DLS), determining the zeta potential, and using cryo-transmitting electron microscopy (cryo-TEM), we reveal the formation of nano-sized, positively charged, and spherical Q-starch complexes. Our results demonstrate that these complexes exhibit efficient cellular uptake, targeting their intended organelles while preserving their physical integrity and functionality. Notably, the intracellular path of the Q-starch/cargo complex is guided by the cargo itself, aligning with its unique biological activity site. This study elucidates the versatility and potency of Q-starch as a versatile drug delivery carrier, paving the way for novel applications offering targeted delivery strategies for potential therapeutic molecules.

Bacterial Outer Membrane‐Based Biomimetic Immune Adaptors: Mild Immunomodulatory and Bacterial Targeted Delivery Strategy Against Implant‐Related Infections

AbstractImplant‐related infections (IRIs) are difficult to manage and are a major cause of surgical failure. The formation of biofilms with a solid barrier on the surface of implants and concomitant suppression of the local immune response constitute major challenges for treating IRIs. This study develops a multifunctional biomimetic immune adaptor (Hybrid Membrane@Levo@SiO2; HMLS) generated by loading the antibiotic levofloxacin (Levo) into silica nanoparticles and coating the particles with a hybrid membrane formed from outer membrane vesicles (OMVs) of Escherichia coli and red blood cell membranes (RBCMs). The HMLS nanoplatform is designed to address the challenges associated with IRIs through a dual‐approach strategy. First, the unique immunogenicity of OMVs regulates the antibacterial immune responses of innate immune cells and reverses the immunosuppressive microenvironment around IRIs. Second, the homotypic targeting effect of OMVs in the hybrid membrane provides HMLS with bacterial targeting functions and efficient bactericidal effects. Additionally, the RBCMs endow the hybrid membrane with mild immunogenicity, which prevents excessive inflammatory stimulation. The synergistic strategy of HMLS exhibits superior antibiofilm effects both in vivo and in vitro, providing a new option for the clinical treatment of refractory IRIs.

T cell-mimicking platelet-drug conjugates

•Platelets act as “Trojan horse” killers to target and inhibit tumor metastasis •Platelet-drug conjugates mimic the natural cytotoxic mechanisms of T cells •Engineered platelets explore the potential of immune-independent cell therapies Cancer metastasis is the leading cause of cancer-related deaths. The indispensable role of platelets in tumor metastasis inspires the targeted delivery strategy by using platelet-drug conjugates (PDCs). Here, we armed platelets with granzyme B and perforin nanocomplexes to suppress cancer metastasis by leveraging the natural cytotoxic mechanism of T cells. Upon systemic administration, PDCs naturally capture circulating tumor cells (CTCs) and actively target nascent metastatic lesions, thus enhancing the targeted delivery efficiency. Subsequently, PDCs activated in situ by tumor cells can produce platelet microparticles (PMPs) that can actively target tumor cells by the expression of adhesion molecules such as P-selectin and thrombospondin-1 (TSP-1) and by secreting cytotoxic protein complexes mimicking cytotoxic lymphocytes. We demonstrated that the PDCs significantly suppressed lung metastasis in two tumor models, B16F10 melanomas and 4T1 breast carcinomas. Cancer metastasis is the leading cause of cancer-related deaths. The indispensable role of platelets in tumor metastasis inspires the targeted delivery strategy by using platelet-drug conjugates (PDCs). Here, we armed platelets with granzyme B and perforin nanocomplexes to suppress cancer metastasis by leveraging the natural cytotoxic mechanism of T cells. Upon systemic administration, PDCs naturally capture circulating tumor cells (CTCs) and actively target nascent metastatic lesions, thus enhancing the targeted delivery efficiency. Subsequently, PDCs activated in situ by tumor cells can produce platelet microparticles (PMPs) that can actively target tumor cells by the expression of adhesion molecules such as P-selectin and thrombospondin-1 (TSP-1) and by secreting cytotoxic protein complexes mimicking cytotoxic lymphocytes. We demonstrated that the PDCs significantly suppressed lung metastasis in two tumor models, B16F10 melanomas and 4T1 breast carcinomas.

Current Strategies for Exosome Cargo Loading and Targeting Delivery

Extracellular vesicles (EVs) such as ectosomes and exosomes have gained attention as promising natural carriers for drug delivery. Exosomes, which range from 30 to 100 nm in diameter, possess a lipid bilayer and are secreted by various cells. Due to their high biocompatibility, stability, and low immunogenicity, exosomes are favored as cargo carriers. The lipid bilayer membrane of exosomes also offers protection against cargo degradation, making them a desirable candidate for drug delivery. However, loading cargo into exosomes remains to be a challenge. Despite various strategies such as incubation, electroporation, sonication, extrusion, freeze–thaw cycling, and transfection that have been developed to facilitate cargo loading, inadequate efficiency still persists. This review offers an overview of current cargo delivery strategies using exosomes and summarizes recent approaches for loading small-molecule, nucleic acid, and protein drugs into exosomes. With insights from these studies, we provide ideas for more efficient and effective delivery of drug molecules by using exosomes.

Regulating lactate-related immunometabolism and EMT reversal for colorectal cancer liver metastases using shikonin targeted delivery

BackgroundThere are few effective medications for treating colorectal cancer and liver metastases (CRLM). The interactions among glycolysis, epithelial-mesenchymal transition (EMT), and immune microenvironment contribute to the progression of CRLM. A main glycolytic enzyme pyruvate Kinase M2 (PKM2) is highly expressed in colorectal cancer and CRLM, and thus can be a potential therapeutic target.MethodsA therapeutic strategy was proposed and the shikonin-loaded and hyaluronic acid-modified MPDA nanoparticles (SHK@HA-MPDA) were designed for CRLM therapy via PKM2 inhibition for immunometabolic reprogramming. The treatment efficacy was evaluated in various murine models with liver metastasis of colorectal tumor.ResultsSHK@HA-MPDA achieved tumor-targeted delivery via hyaluronic acid-mediated binding with the tumor-associated CD44, and efficiently arrested colorectal tumor growth. The inhibition of PKM2 by SHK@HA-MPDA led to the remodeling of the tumor immune microenvironment and reversing EMT by lactate abatement and the suppression of TGFβ signaling; the amount of cytotoxic effector CD8+ T cells was increased while the immunosuppressive MDSCs decreased.ConclusionThe work provided a promising targeted delivery strategy for CRLM treatment by regulating glycolysis, EMT, and anticancer immunity.Graphic abstractAn immunometabolic strategy for treating colorectal cancer liver metastases using the shikonin-loaded, hyaluronic acid-modified mesoporous polydopamine nanoparticles (SHK@HA-MPDA) via glycolysis inhibition, anticancer immunity activation, and EMT reversal. SHK@HA-MPDA can inhibit cytoplasmic PKM2 and glycolysis of the tumor and reduce lactate flux, and then activate the DCs and remodel the tumor immune microenvironment. The reduced lactate flux can reduce MDSC migration and suppress EMT.

Angiopep-2-conjugated FeTi@Au core-shell nanoparticles for tumor targeted dual-mode magnetic resonance imaging and hyperthermic glioma therapy

Herein, we fabricated gold surface-coated iron titanium core-shell (FeTi@Au) nanoparticles (NPs) with conjugation of angiopep-2 (ANG) (FeTi@Au-ANG) NPs for targeted delivery and improved NPs penetration by receptor-mediated endocytosis to achieve hyperthermic treatment of gliomas. The synthesized “core-shell” FeTi@Au-ANG NPs exhibited spherical in shape with around 16 nm particle size and increased temperature upon alternating magnetic field (AMF) stimulation, rendering them effective for localized hyperthermic therapy of cancer cells. Effective targeted delivery of FeTi@Au-ANG NPs was demonstrated in vitro by improved transport and cellular uptake, and increased apoptosis in glioma cells (C6) compared with normal fibroblast cells (L929). FeTi@Au-ANG NPs exhibited higher deposition in brain tissues and a superior therapeutic effect in an orthotopic intracranial xenograft mouse model. Taken together, our data indicate that FeTi@Au-ANG NPs hold significant promise as a targeted delivery strategy for glioma treatment using hyperthermia.

Glutamine coated titanium for synergistic sonodynamic and photothermal on tumor therapy upon targeted delivery.

Introduction: The application of titanium dioxide nanoparticles (TiO2 NPs) for cancer therapy has been studied for decades; however, the targeted delivery of TiO2 NPs to tumor tissues is challenging, and its efficiency needs to be improved. Method: In this study, we designed an oxygen-deficient TiO2-x coated with glutamine layer for targeted delivery, as well as the enhanced separation of electrons (e-) and holes (h+) following the joint application of sonodynamic therapy (SDT) and photothermal therapy (PTT). Results: This oxygen-deficient TiO2-x possesses relatively high photothermal and sonodynamic efficiency at the 1064nm NIR-II bio-window. The GL-dependent design eased the penetration of the TiO2-x into the tumor tissues (approximately three-fold). The in vitro and in vivo tests showed that the SDT/PTT-based synergistic treatment achieved more optimized therapeutic effects than the sole use of either SDT or PTT. Conclusion: Our study provided a safety targeted delivery strategy, and enhanced the therapeutic efficiency of SDT/PTT synergistic treatment.

Developing non-viral or viral vectors for efficient and targeted delivery of genetic material, such as DNA or RNA, for gene therapy applications

Gene therapy has emerged as a promising approach for treating a wide range of genetic and acquired diseases by introducing or modifying genetic material within cells. To achieve successful gene therapy, efficient and precise delivery of genetic material, such as DNA or RNA, to target cells is essential. This abstract explores the development of both non-viral and viral vectors for the delivery of genetic material in gene therapy applications. Non-viral vectors, including lipid nanoparticles (LNPs), polymer-based carriers, and cell-penetrating peptides, have gained significant attention due to their safety profile and ease of production. These vectors are designed to protect genetic material from degradation, facilitate cellular uptake, and release the cargo at the desired location. Recent advancements in nanotechnology have enabled the design of customizable non-viral vectors with enhanced delivery efficiency and reduced offtarget effects. Viral vectors, on the other hand, harness the natural infectivity of viruses to transport genetic material into target cells. Retroviruses, lentiviruses, adenoviruses, and adeno-associated viruses (AAVs) are commonly used viral vectors in gene therapy. Viral vectors offer high transduction efficiency but may trigger immune responses or pose risks of insertional mutagenesis. Efforts in vector engineering have led to the development of safer viral vectors with improved targeting capabilities and reduced immunogenicity. AAVs, in particular, have gained prominence due to their ability to achieve long-lasting gene expression with minimal adverse effects. Targeted delivery strategies aim to enhance vector specificity, ensuring that genetic material reaches the intended cell type or tissue. These strategies include modifying vector surface proteins, employing tissue-specific promoters, or utilizing ligand-receptor interactions. In conclusion, the successful application of gene therapy relies on the development of efficient and targeted delivery systems for genetic material. Non-viral and viral vectors offer distinct advantages and continue to evolve to meet the demands of gene therapy applications. Advances in vector design, safety, and targeting strategies hold promise for the continued progress of gene therapy as a transformative medical intervention.

Heparin-Coated Dendronized Hyperbranched Polymers for Antimalarial Targeted Delivery.

The rampant evolution of resistance in Plasmodium to all existing antimalarial drugs calls for the development of improved therapeutic compounds and of adequate targeted delivery strategies for them. Loading antimalarials in nanocarriers specifically targeted to the parasite will contribute to the administration of lower overall doses, with reduced side effects for the patient, and of higher local amounts to parasitized cells for an increased lethality toward the pathogen. Here, we report the development of dendronized hyperbranched polymers (DHPs), with capacity for antimalarial loading, that are coated with heparin for their specific targeting to red blood cells parasitized by Plasmodium falciparum. The resulting DHP-heparin complexes exhibit the intrinsic antimalarial activity of heparin, with an IC50 of ca. 400 nM, added to its specific targeting to P. falciparum-infected (vs noninfected) erythrocytes. DHP-heparin nanocarriers represent a potentially interesting contribution to the limited family of structures described so far for the loading and targeted delivery of current and future antimalarial compounds.

Tyrosine Kinase Inhibitors for Glioblastoma Multiforme: Challenges and Opportunities for Drug Delivery.

Glioblastoma multiforme (GBM) is an aggressive brain tumor with high mortality rates. Due to its invasiveness, heterogeneity, and incomplete resection, the treatment is very challenging. Targeted therapies such as tyrosine kinase inhibitors (TKIs) have great potential for GBM treatment, however, their efficacy is primarily limited by poor brain distribution due to the presence of the blood-brain barrier (BBB). This review focuses on the potential of TKIs in GBM therapy and provides an insight into the reasons behind unsuccessful clinical trials of TKIs in GBM despite the success in treating other cancer types. The main section is dedicated to the use of promising drug delivery strategies for targeted delivery to brain tumors. Use of brain targeted delivery strategies can help enhance the efficacy of TKIs in GBM. Among various drug delivery approaches used to bypass or cross BBB, utilizing nanocarriers is a promising strategy to augment the pharmacokinetic properties of TKIs and overcome their limitations. This is because of their advantages such as the ability to cross BBB, chemical stabilization of drug in circulation, passive or active targeting of tumor, modulation of drug release from the carrier, and the possibility to be delivered via non-invasive intranasal route.