Multifunctional theranostic nanoplatforms enabling precise targeting and controlled deep tissue therapy are vital. Herein, we present a self-assembled, defect-engineered, biomimetic nanoplatform (CDMBBTO), in which piezoelectric material and downconversion nanoparticles (DCNPs) are co-assembled within a polymer matrix, preventing interactions between both components, thereby allowing each to retain its intrinsic properties while collectively enabling dual second near infrared fluorescence (NIR-II FL)/magnetic resonance (MR) imaging and synergistic piezo/chemodynamic therapy (PZDT/CDT). Mn/Bi codoped piezoelectric BaTiO3 (MBBTO) NPs exhibit a significantly enhanced piezoelectric coefficient ( 5 fold higher than pristine BTO) owing to bandgap modulation induced by defect engineering. The incorporated Mn2+ not only catalyzes Fenton like reactions for sustained tumor suppression but also provides strong T2 weighted MR contrast. Self-assembled NIR-II emissive DCNPs enable deep tissue optical imaging, forming an integrated theranostic system. Cloaking of U87 glioma cell membranes imparts homologous tumor targeting capability. In vivo dual modal imaging reveals efficient tumor accumulation, with peak NIR-II FL and MR signal intensities observed 6 h post-injection. Upon ultrasound activation, CDMBBTO elicits potent tumor ablation through synergistic reactive oxygen species generation and immune modulation, characterized by macrophage polarization (M2 → M1) and upregulation of proinflammatory cytokines (TNF-α and IL-6). This work establishes CDMBBTO as a powerful nanoplatform for dual modal imaging-guided, immune potentiated PZDT/CDT toward effective glioblastoma treatment.

Early diagnosis of brain tumors is challenging due to their complexity and delicate structure. Conventional imaging techniques like MRI, CT, and PET are unable to provide detailed visualization of early-stage brain tumors. Early-stage detection of brain tumors is vital for enhancing patient outcomes and survival rates. So far, several scientists have dedicated their efforts to innovating advanced diagnostic probes to efficiently cross the BBB and selectively target brain tumors for optimal imaging. The integration of these techniques presents a viable pathway for non-invasive, accurate, and early-stage tumor identification. Herein, we provide a timely update on the various imaging probes and potential challenges for the diagnosis of early-stage brain tumors. Furthermore, this review highlights the significance of integrating advanced imaging probes for improving the early detection of brain tumors, ultimately enhancing treatment outcomes. Hopefully, this review will stimulate the interest of researchers to accelerate the development of new imaging probes and even their clinical translation for improving the early diagnosis of brain tumors.

Breast cancer has a high mortality rate and is one of the most common malignancies among women. Conventional therapies such as radiotherapy, chemotherapy, and surgery are not sufficiently effective and have notable drawbacks, including toxicity and damage to healthy cells, resulting in an unsatisfactory prognosis. Photothermal therapy (PTT) and combinatory therapies have emerged as a promising therapeutic paradigm for breast cancer treatment to achieve precise, minimally invasive tumor ablation with real-time imaging guidance, synergistic therapeutic effects, reduced systemic toxicity, enhanced immune activation, and improved outcomes against recurrence, metastasis, and drug resistance. These approaches utilize near-infrared light to visualize tumor margins and locally generate hyperthermia to destroy cancerous tissue. The development of novel nanomaterials has significantly enhanced the efficacy of breast cancer treatments. This review explores the mechanisms, current advancements, and clinical potential of PTT and combinatory therapy in breast cancer treatment, with an emphasis on developments to a three-level progression: material innovation, targeted delivery, and multimodal synergy. Special focus is given to the rapidly advancing image-guided PTT in combination with other treatment modalities for precise and effective treatment of breast cancer. Furthermore, the review addresses the challenges and future directions in translating these technologies from preclinical models to clinical settings, including the optimization of imaging resolution and thermal efficiency, while minimizing potential side effects. We hope this perspective offers valuable insights into PTT and combinatory therapies for breast cancer and contributes to advancing their clinical translation, ultimately enhancing women's health.

Recent studies demonstrate that NIR-II fluorescence imaging-guided photodynamic therapy (PDT) is a promising paradigm for cancer theranostics, but its efficacy is suboptimal due to limited light penetration and oxygen dependence. Emerging piezodynamic therapy (PZDT) can overcome the shortcomings of PDT and shows merits including deep penetration, oxygen independence, and efficient reactive oxygen species (ROS) generation. Integration of NIR-II fluorescence and PZDT can revolutionize cancer theranostics with greatly improved efficacy. However, it is difficult to achieve because of the optical darkness of piezoelectric materials. Herein, defect-engineered NIR-II transparent Gd-doped KNbO3 (GKNO) coating on NIR-II fluorescent NaGd0.65F4@Nd0.05Yb0.25Er0.05 downconversion nanocores, forming multifunctional nanoplatforms (DGKNO) for dual NIR-II fluorescence/MR imaging-guided PZDT. Importantly, Gd3+ doping introduces interstitial defects in the KNO lattice, imparting MRI capability, bandgap widening, tenfold enhancement in piezoelectric coefficient, and enhanced ROS generation. Notably, bandgap widening enhanced NIR-II transparency up to 96%, enabling effective NIR-II fluorescence imaging. Furthermore, finite element analysis and first-principle calculations validate the boosted piezoelectric effect and transparency. After cloaking with U87 glioma cell membranes to yield biomimetic nanoplatforms (CDGKNO), intravenous administration enabled NIR-II fluorescence/MRI-guided PZDT, inducing ROS-mediated oxidative stress and macrophage polarization (M2 to M1), achieving efficient tumor inhibition. This work demonstrates dual NIR-II fluorescence/MRI-guided PZDT as a powerful paradigm for cancer treatment.

Metastatic breast cancer (MBC) remains one of the most aggressive and fatal malignancies in women, primarily due to tumor heterogeneity, multidrug resistance, and the limitations of conventional therapeutic approaches. Aim: This review aims to evaluate recent advances in nanomaterial-based photothermal therapy (PTT) platforms and their potential in the treatment of metastatic breast cancer. Method: A comprehensive analysis of current literature was conducted to examine how various nanomaterials are engineered for targeted PTT, with particular emphasis on their mechanisms of action, synergistic applications with chemotherapy, immunotherapy, and photodynamic therapy, as well as their capacity to overcome challenges associated with targeting metastatic niches. Results: The findings indicate that nanotechnology-enabled PTT provides spatiotemporal precision, efficient tumor ablation, and reduced systemic toxicity, while significantly enhancing therapeutic outcomes when integrated into multimodal treatment strategies. Recent preclinical studies and early clinical trials further underscore advancements in imaging guidance, thermal efficiency, and site-specific drug delivery; however, issues related to biocompatibility, safety, and large-scale clinical translation remain unresolved. Conclusions: Nanomaterial-assisted PTT holds substantial promise for improving therapeutic efficacy against metastatic breast cancer. Future research should prioritize optimizing imaging resolution, minimizing adverse effects, and addressing translational challenges to accelerate clinical integration and ultimately enhance health outcomes for women.

Antibiotic-resistant bacteria often cause lethal infections in both the surficial and deep organs of humans. Failure of antibiotics in resistant infections leads to more effective alternative therapies, like spatiotemporally controllable piezodynamic therapy (PZDT) with deep penetration. Currently, PZDT demands further investigation for improved treatment outcomes and the corresponding therapeutic mechanisms. Herein, a nanocomposite cloaked is reported with a biomimetic coating of TLR-upregulated macrophage membrane for targeted PZDT against MRSA-induced skin wound infection and osteomyelitis, representing surficial and deep infection models, respectively. To boost the therapeutic efficacy, crystal defect engineering is applied by impregnating Fe2+ into bismuth oxy-iodide nanosheets to increase the crystal defects. This results in a significantly higher piezoelectric coefficient than in previous reports, contributing to an amplified reactive oxygen species generation for bacterial killing. More importantly, the notable piezoelectric effect not only re-programs the macrophages into an anti-inflammatory M2 phenotype for accelerating bacterial wound healing but also stimulates the opening of the piezo-stimulated Ca2+ channels and boosts the differentiation of mesenchymal stem cells into osteoblasts for expediting bone tissue repair in osteomyelitis model. Moreover, the Fe-doping supplements T2-magnetic resonance imaging for real-time visualization of nanocomposite distribution. This theranostic system opens a new avenue for future treatment of drug-resistant bacteria-caused diseases.

The progress in nanobiohybrids empowered by modified bacteria and vesicles for cancer treatment is systematically updated.

Despite advancements in the treatment of glioblastoma, it faces challenges due to tumor heterogeneity, the blood-brain barrier, recurrence, immune evasion, and conventional strategies, leading to low survival and a poor prognosis. Therefore, it is crucial to develop novel, useful treatment strategies for improving brain distribution to overcome blood-brain barriers (BBB) and help the treatment of glioblastoma. Conventional immunotherapy like checkpoint inhibitors, CAR-T cell therapy, monoclonal antibodies, cancer vaccines, and adoptive cell transfer often suffers from low therapeutic outcomes because the singular therapy generally has shortcomings, such as the cold immune microenvironment of brain tumors. In contrast, the emerging combinatory immunotherapy integrated with chemo-immunotherapy, photothermal-immunotherapy, and radio-immunotherapy has shown great promise to modulate tumoral immune microenvironment and boost treatment outcomes. This review discusses the immune microenvironment of GBM, its impact on immunological effects, current immunotherapy methods, and advanced studies. It also introduces combinational GBM immunotherapy with traditional cancer therapies like chemo-immunotherapy, surgery-immunotherapy, photothermal-immunotherapy, and radiotherapy-immunotherapy. In the future, it is anticipated that this article will provide beneficial information and a path for the strategy of innovative, efficient combination immunotherapy in the treatment of glioblastoma.

Significance: Reactive oxygen species (ROS) are crucial signaling molecules in the regulation of numerous physiological activities including the formation and function of the central nervous system (CNS). So far, many functional antioxidant nanomedicines with ROS scavenging capability to reduce oxidative stress in Alzheimer's disease (AD) have been developed for both imaging and therapy of AD. Recent Advances: This review focuses on the most recent advances in antioxidant nanomedicines such as ROS-scavenging nanoparticles (NPs), NPs with intrinsic antioxidant activity, and drug-loaded antioxidant NPs for AD theranostics. In addition to antioxidant nanomedicines, the emerging phototherapy treatment paradigms and the promising preclinic drug carriers, such as exosomes and liposomes, are also introduced. Critical Issues: In general, excessive generation of ROS can cause lipid peroxidation, oxidative DNA, as well as protein damage, aggravating pathogenic alterations, accumulation of amyloid-beta plaques and neurofibrillary tangles in the brain. These negative factors further cause cell death, which is the beginning of AD. Future Directions: We anticipate that this review will help researchers in the area of preclinical research and clinical translation of antioxidant nanomedicines for AD imaging and therapy.

As the second-leading cause of human death, cancer has drawn attention in the area of biomedical research and therapy from all around the world. Certainly, the development of nanotechnology has made it possible for nanoparticles (NPs) to be used as a carrier for delivery systems in the treatment of tumors. This is a biomimetic approach established to craft remedial strategies comprising NPs cloaked with membrane obtained from various natural cells like blood cells, bacterial cells, cancer cells, etc. Here we conduct an in-depth exploration of cell membrane-coated NPs (CMNPs) and their extensive array of applications including drug delivery, vaccination, phototherapy, immunotherapy, MRI imaging, PET imaging, multimodal imaging, gene therapy and a combination of photothermal and chemotherapy. This review article provides a thorough summary of the most recent developments in the use of CMNPs for the diagnosis and treatment of cancer. It critically assesses the state of research while recognizing significant accomplishments and innovations. Additionally, it indicates ongoing problems in clinical translation and associated queries that warrant deeper research. By doing so, this study encourages creative thinking for future projects in the field of tumor therapy using CMNPs while also educating academics on the present status of CMNP research. Illustration shows the various sources of cell membrane along with different NPs used for the production of cell membrane-coated nanoparticles and their applications.

Cancer is measured as a major threat to human life and is a leading cause of death. Millions of cancer patients die every year, although a burgeoning number of researchers have been making tremendous efforts to develop cancer medicine to fight against cancer. Owing to the complexity and heterogeneity of cancer, lack of ability to treat deep tumor tissues, and high toxicity to the normal cells, it complicates the therapy of cancer. However, bacterial derivative-mediated drug delivery has raised the interest of researchers in overcoming the restrictions of conventional cancer chemotherapy. In this review, we show various examples of tumor-targeting bacteria and bacterial derivatives for the delivery of anticancer drugs. This review also describes the advantages and limitations of delivering anticancer treatment drugs under regulated conditions employing these tumor-targeting bacteria and their membrane vesicles. This study highlights the substantial potential for clinical translation of bacterial-based drug carriers, improve their ability to work with other treatment modalities, and provide a more powerful, dependable, and distinctive tumor therapy.

Glioblastoma (GBM) treatment is still a big clinical challenge because of its highly malignant, invasive, and lethal characteristics. After treatment with the conventional therapeutic paradigm of surgery combined with radio- and chemotherapy, patients bearing GBMs generally exhibit a poor prognosis, with high mortality and a high disability rate. The main reason is the existence of the formidable blood-brain barrier (BBB), aggressive growth, and the infiltration nature of GBMs. Especially, the BBB suppresses the delivery of imaging and therapeutic agents to lesion sites, and thus this leads to difficulties in achieving a timely diagnosis and treatment. Recent studies have demonstrated that extracellular vesicles (EVs) exhibit favorable merits including good biocompatibility, a strong drug loading capacity, long circulation time, good BBB crossing efficiency, specific targeting to lesion sites, and high efficiency in the delivery of a variety of cargos for GBM therapy. Importantly, EVs inherit physiological and pathological molecules from the source cells, which are ideal biomarkers for molecularly tracking the malignant progression of GBMs. Herein, we start by introducing the pathophysiology and physiology of GBMs, followed by presenting the biological functions of EVs in GBMs with a special focus on their role as biomarkers for GBM diagnosis and as messengers in the modulation of the GBM microenvironment. Furthermore, we provide an update on the recent progress of using EVs in biology, functionality, and isolation applications. More importantly, we systematically summarize the most recent advances of EV-based carriers for GBM therapy by delivering different drugs including gene/RNA-based drugs, chemotherapy drugs, imaging agents, and combinatory drugs. Lastly, we point out the challenges and prospects of future research on EVs for diagnosing and treating GBMs. We hope this review will stimulate interest from researchers with different backgrounds and expedite the progress of GBM treatment paradigms.

Nowadays, a malignant brain tumor is one of the most life-threatening diseases with poor prognosis, high risk of recurrence, and low survival rate for patients because of the existence of the blood-brain barrier (BBB) and the lack of efficient diagnostic and therapeutic paradigms. So far, many researchers have devoted their efforts to innovating advanced drugs to efficiently cross the BBB and selectively target brain tumors for optimal imaging and therapy outcomes. Herein, we update the most recent developments in nanomedicines for the diagnosis and treatment of brain tumors in preclinical mouse models. The special focus is on burgeoning drug delivery carriers to improve the specificity of visualization and to enhance the efficacy of brain tumor treatment. Also, we highlight the challenges and perspectives for the future development of brain tumor theranostics. This review is expected to receive wide attention from researchers, professors, and students in various fields to participate in future advancements in preclinical research and clinical translation of brain tumor nanomedicines.

Fluorescence imaging in the second near-infrared window (NIR-II) has become a prevalent choice owing to its appealing advantages like deep penetration depth, low autofluorescence, decent spatiotemporal resolution, and a high signal-to-background ratio. This would expedite the innovation of NIR-II imaging-guided drug delivery (IGDD) paradigms for the improvement of the prognosis of patients with tumors. This work systematically reviews the recent progress of such NIR-II IGDD-mediated cancer therapeutics and collectively brings its essence to the readers. Special care has been taken to assess their performances based on their design approach, such as enhancing their drug loading and triggering release, designing intrinsic and extrinsic fluorophores, and/ or overcoming biological barriers. Besides, the state-of-the-art NIR-II IGDD platforms for different therapies like chemo-, photodynamic, photothermal, chemodynamic, immuno-, ion channel, gas-therapies, and multiple functions such as stimulus-responsive imaging and therapy, and monitoring of drug release and therapeutic response, have been updated. In addition, for boosting theranostic outcomes and clinical translation, the innovation directions of NIR-II IGDD platforms are summarized, including renal-clearable, biodegradable, sub-cellular targeting, and/or afterglow, chemiluminescence, X-ray excitable NIR-IGDD, and even cell therapy. This review will propel new directions for safe and efficient NIR-II fluorescence-mediated anticancer drug delivery.

Parkinson's disease (PD) is a chronic, and highly neurodegenerative disorder with complex pathological processes. The features for neuropathological identification of PD include a-synuclein (a-syn) protein aggregates, oxidative stress, metal ion dyshomeostasis, neurotransmitter deficiencies, and mitochondrial dysfunction. Currently, no definite treatment paradigm can completely cure PD patients, which is increasing globally over the past few decades. The existence of the blood-brain barrier (BBB) restricts the conventional treatment processes and makes the therapeutic delivery to the brain a bit more challenging. Therefore, developing new useful medicines for improving brain distribution is vital to overcome BBB and helping the early diagnosis and treatment of PD. In this review, the current limitations of conventional drugs are highlighted and the development of new medicines to overcome such limitations is covered. This work will provide insight into the direction for designing novel efficient nanomedicines for the early diagnosis and treatment of PD.

Glioblastoma (GBM) is a challenging problem due to the poor BBB permeability of cancer drugs, its recurrence after the treatment, and high malignancy and is difficult to treat with the currently available therapeutic strategies. Furthermore, the prognosis and survival rate of GBM are still poor after surgical removal via conventional combination therapy. Owing to the existence of the formidable blood-brain barrier (BBB) and the aggressive, infiltrating nature of GBM growth, the diagnosis and treatment of GBM are quite challenging. Recently, liposomes and their derivatives have emerged as super cargos for the delivery of both hydrophobic and hydrophilic drugs for the treatment of glioblastoma because of their advantages, such as biocompatibility, long circulation, and ease of physical and chemical modification, which facilitate the capability of targeting specific sites, circumvention of BBB transport restrictions, and amplification of the therapeutic efficacy. Herein, we provide a timely update on the burgeoning liposome-based drug delivery systems and potential challenges in these fields for the diagnosis and treatment of brain tumors. Furthermore, we focus on the most recent liposome-based drug delivery cargos, including pH-sensitive, temperature-sensitive, and biomimetic liposomes, to enhance the multimodality in imaging and therapeutics of glioblastoma. Furthermore, we highlight the future difficulties and directions for the research and clinical translation of liposome-based drug delivery. Hopefully, this review will trigger the interest of researchers to expedite the development of liposome cargos and even their clinical translation for improving the prognosis of glioblastoma.

As the second-leading cause of human death, cancer has drawn attention to the area of biomedical research and therapy from all around the world. Certainly, the development of nanotechnology has...

Illustration shows the various sources of cell membrane along with different NPs used for the production of cell membrane-coated nanoparticles and their applications.

Misuse and overuse of antibiotics led us vulnerable to multi-drug resistant (MDR) bacteria, biofilms, and intracellular infections. The failure of conventional antibiotics thus gives rise to numerous novel nanoth-erapeutics such as dynamic therapies, immuno-and gene therapies, antibiotic and peptide delivery. These alternative therapies could save humanity from severe infectious diseases. Henceforth, a critical review is much needed to timely abridge the progress and challenges of these nanotherapeutics. This review initially aims to describe the mechanisms behind multi-drug resistance and its devastating effects on human health. Later, a discussion has been made on why conventional antibiotics are failed and how the scientific fraternity has come forward to deliver nanoparticle (NP)-based new technologies to erad-icate bacterial infections. These methods are new and need rigorous attention for advancement. Apart from bacteriology, these modalities can perform well in cancer biology and other biomedical fields as well. Thus, a topical review of such nano-therapies could open new avenues in numerous branches of biomedical engineering under a wider spectrum, which may evolve new ideas and directions. We hope this review will inspire and motivate researchers to develop novel nanomaterials for antibacterial activity and bring sustainable clinical success against MDR bacteria in the coming years. (c) 2023 Elsevier B.V. All rights reserved.

Nowadays, malignant brain tumors are still mostly lethal diseases with poor prognosis and a clinical median survival rate of fewer than 2 years after therapeutic intervention. It is difficult to achieve complete remission of brain tumors due to blood-brain barrier (BBB) and a lack of efficient drug delivery systems to targeted transportation of brain tumor medicines. Nanoparticle delivery systems have shown merits including stability and high carrier capacity for the transportation of different drugs to treat brain tumors. The application of mRNA nanomedicines brings in great promise not only in COVID-19, but also for malignant brain tumor immunotherapy. The appropriate delivery system facilitates mRNA delivery efficiency and enhances the immune response successfully, for optimal treatment outcomes on malignant brain tumors. Herein, we do an updated review on the development of mRNA nanomedicines for malignant brain cancer treatment. We focus on how to design mRNA-loaded nanoparticle-based delivery systems with optimized pharmacokinetics and pharmacodynamics for efficient therapy of brain cancers. In addition, we point out the challenges and solutions for further development of mRNA nanomedicines for brain cancer therapy. We hope this review would stimulate interest among researchers with different backgrounds and expedite the translation from bench to bedside for the mRNA nanomedicines.