Development Of Nanomedicines Research Articles

TRAIL-driven targeting and reversing cervical cancer radioresistance by seleno-nanotherapeutics through regulating cell metabolism

Recently, radioresistance has become a major obstacle in the radiotherapy of cervical cancer. To demonstrate enhanced radiosensitization against radioresistant cervical cancer, radioresistant cervical cancer cell line was developed and the mechanism of radioresistance was explored. Due to the overexpression of (death receptor 5, DR5) in cervical cancer, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-overexpressed cervical cancer cell membrane-camouflaged Cu2−xSe nanomedicine (CCMT) was designed. Since the CCMT was encapsulated with TRAIL-modified cell membrane, it represented high target to cervical cancer cell and immune evasion. Furthermore, Cu2−xSe had the ability to scavenge glutathione (GSH) and produce ·OH with excess H2O2 in the tumor microenvironment. The presence of CCMT combined with radiation therapy could effectively increase the 1O2 produced by X-rays. In vitro and in vivo studies elaborated that CCMT exhibited excellent radiosensitization properties to reverse radiotolerance by scavenging GSH and promoting DNA damage, apoptosis, mitochondrial membrane potential damage and metabolic disruption. Collectively, this study suggested that the development of TRAIL-overexpressed cell membrane-camouflaged Cu2−xSe nanomedicine could advance future cervical cancer treatment and minimize the disadvantages associated with radiation treatment.

Fixation and Visualization of Full Protein Corona on Lipid Surface of Composite Nanoconstruction.

Spontaneous sorption of proteins on the nanoparticles' surface leads to the fact that nanoparticles in biological media are always enveloped by a layer of proteins-the protein corona. Corona proteins affect the properties of nanoparticles and their behavior in a biological environment. In this regard, knowledge about the composition of the corona is a necessary element for the development of nanomedicine. Because proteins have different sorption efficacy, isolating particles with a full corona and characterizing the full corona is challenging. In this study, we propose a photo-activated cross-linker for full protein corona fixation. We believe that the application of our proposed approach will make it possible to capture and visualize the full corona on nanoparticles coated with a lipid shell.

Future Trends in Pharmaceuticals: Investigation of the Role of AI in Drug Discovery, 3D Printing of Medications, and Nanomedicine

The pharmaceutical sector has to deal with issues like high costs, difficult diseases, and the demand for tailored therapy. The transformational potential of AI, 3D printing, and nanomedicine is examined in this paper. Drug development is revolutionized by AI, which also predicts effectiveness and personalizes therapies. Tailors, prescriptions, and complex documents can all be 3D printed to help with compliance. Nanoparticles are used in nanomedicine to deliver drugs more precisely and enhance solubility. Future themes include AI-driven target identification and individualized treatment; the effectiveness and role of 3D printing in personalized medicine; and improved medication delivery through nanomedicine. These developments promise to alter healthcare, which will help a lot of people. The study results offers a thorough examination of upcoming trends in the pharmaceutical industry and similarly discusses developments in 3D printing and nanomedicine.

Impact of the physical-chemical properties of poly(lactic acid)–poly(ethylene glycol) polymeric nanoparticles on biodistribution

Nanoparticle (NP) formulations are inherently polydisperse making their structural characterization and justification of specifications complex. It is essential, however, to gain an understanding of the physico-chemical properties that drive performance in vivo. To elucidate these properties, drug-containing poly(lactic acid) (PLA)–poly(ethylene glycol) (PEG) block polymeric NP formulations (or PNPs) were sub-divided into discrete size fractions and analyzed using a combination of advanced techniques, namely cryogenic transmission electron microscopy, small-angle neutron and X-ray scattering, nuclear magnetic resonance, and hard-energy X-ray photoelectron spectroscopy. Together, these techniques revealed a uniquely detailed picture of PNP size, surface structure, internal molecular architecture and the preferred site(s) of incorporation of the hydrophobic drug, AZD5991, properties which cannot be accessed via conventional characterization methodologies. Within the PNP size distribution, it was shown that the smallest PNPs contained significantly less drug than their larger sized counterparts, reducing overall drug loading, while PNP molecular architecture was critical in understanding the nature of in vitro drug release. The effect of PNP size and structure on drug biodistribution was determined by administrating selected PNP size fractions to mice, with the smaller sized NP fractions increasing the total drug-plasma concentration area under the curve and reducing drug concentrations in liver and spleen, due to greater avoidance of the reticuloendothelial system. In contrast, administration of unfractionated PNPs, containing a large population of NPs with extremely low drug load, did not significantly impact the drug's pharmacokinetic behavior - a significant result for nanomedicine development where a uniform formulation is usually an important driver. We also demonstrate how, in this study, it is not practicable to validate the bioanalytical methodology for drug released in vivo due to the NP formulation properties, a process which is applicable for most small molecule-releasing nanomedicines. In conclusion, this work details a strategy for determining the effect of formulation variability on in vivo performance, thereby informing the translation of PNPs, and other NPs, from the laboratory to the clinic.

Poly(ethyl ethylene phosphate): Overcoming the "Polyethylene Glycol Dilemma" for Cancer Immunotherapy and mRNA Vaccination.

Polyethylene glycol conjugation (PEGylation) is the most successful strategy to promote the stability, pharmacokinetics, and efficacy of therapeutics; however, anti-PEG antibodies induced by repeated treatments raise serious concerns about the future of PEGylated therapeutics. In order to solve the "PEG dilemma", polymers with excellent water solubility and biocompatibility are urgently desired to attenuate the generation of anti-PEG antibodies. Here, poly(ethyl ethylene phosphate) (PEEP) with excellent degradability and stealth effects is used as an alternative to PEG to overcome the "PEG dilemma". PEEPylated liposomes exhibit lower immunogenicity and generate negligible anti-PEEP antibodies (IgM and IgG) after repeated treatments. In vivo studies confirm that PEEPylated liposomes loaded with oxaliplatin (PEEPlipo@OxPt) show better pharmacokinetics compared to PEGlipo@OxPt, and they exhibit potent antitumor performances, which can be further promoted with checkpoint blockade immunotherapy. In addition, PEEPylated lipid nanoparticle is also used to develop an mRNA vaccine with the ability to evoke a potent antigen-specific T cell response and achieve excellent antitumor efficacy. PEEP shows promising potentials in the development of next-generation nanomedicines and vaccines with higher safety and efficacy.

Recent developments in chemodrug-loaded nanomedicines and their application in combination cancer immunotherapy

Recent developments in chemodrug-loaded nanomedicines and their application in combination cancer immunotherapy

Covalent Organic Frameworks: Opportunities for Rational Materials Design in Cancer Therapy.

Nanomedicines are extensively used in cancer therapy. Covalent organic frameworks (COFs) are crystalline organic porous materials with several benefits for cancer therapy, including porosity, design flexibility, functionalizability, and biocompatibility. This review examines the use of COFs in cancer therapy from the perspective of reticular chemistry and function-oriented materials design. First, the modification sites and functionalization methods of COFs are discussed, followed by their potential as multifunctional nanoplatforms for tumor targeting, imaging, and therapy by integrating functional components. Finally, some challenges in the clinical translation of COFs are presented with the hope of promoting the development of COF-based anticancer nanomedicines and bringing COFs closer to clinical trials.

Comparison effects of Ferula gummosa essential oil and Beta-pinene Alginate nanoparticles on human melanoma and breast cancer cells proliferation and apoptotic index in short term normobaric hyperoxic model

BackgroundBreast cancer is the most common cancer among women, and melanoma is the most dreadful type of skin cancer. Due to the side effects of chemotherapy drugs, the development of new herbal nano-medicines has been considered.MethodsThis study first investigated the chemical composition of Ferula gummosa essential oil using GC-MS analysis; β-pinene, with 61.57%, was the major compound. Next, alginate nanoparticles containing β-pinene and the essential oil with particle sizes of 174 ± 7 and 137 ± 6 nm were prepared. Meanwhile, their zeta potentials were 12.4 ± 0.7 and 28.1 ± 1 mV. Besides, the successful loading of β-pinene and the essential oil in nanoparticles was confirmed using ATR-FTIR analysis. After that, their effects on viability and apoptotic index of human melanoma and breast cancer cells were investigated in normoxia and normobaric hyperoxia (NBO) conditions.ResultsThe best efficacy on A-375 and MDA-MB-231 cells was achieved by alginate nanoparticles containing the EO at hyperoxic and normoxia conditions; IC50 76 and 104 µg/mL. Besides, it affected apoptosis-involved genes; as Bax/Bcl-2 ratio was higher than 1, conditions for induction of apoptosis were obtained. Higher sensitivity was observed in the A-375 cell line treated with Alg-EO in the NBO model.ConclusionsAlginate nanoparticles containing F. gummosa EO could be considered for further investigation in anticancer studies. Also, it may be expected that NBO can be a new strategy for delaying cancer progression and improving nanotherapy efficacy.

Mangifera indica L., By-Products, and Mangiferin on Cardio-Metabolic and Other Health Conditions: A Systematic Review.

Mango and its by-products have traditional medicinal uses. They contain diverse bioactive compounds offering numerous health benefits, including cardioprotective and metabolic properties. This study aimed to explore the impact of mango fruit and its by-products on human health, emphasizing its metabolic syndrome components. PUBMED, EMBASE, COCHRANE, and GOOGLE SCHOLAR were searched following PRISMA guidelines, and the COCHRANE handbook was utilized to assess bias risks. In vivo and in vitro studies have shown several benefits of mango and its by-products. For this systematic review, 13 studies met the inclusion criteria. The collective findings indicated that the utilization of mango in various forms-ranging from fresh mango slices and mango puree to mango by-products, mango leaf extract, fruit powder, and mangiferin-yielded many favorable effects. These encompassed enhancements in glycemic control and improvements in plasma lipid profiles. Additionally, mango reduces food intake, elevates mood scores, augments physical performance during exercise, improves endothelial function, and decreases the incidence of respiratory tract infections. Utilizing mango by-products supports the demand for healthier products. This approach also aids in environmental conservation. Furthermore, the development of mango-derived nanomedicines aligns with sustainable goals and offers innovative solutions for healthcare challenges whilst being environmentally conscious.

Nanomedicine Combats Drug Resistance in Lung Cancer.

Lung cancer is the second most prevalent cancer and the leading cause of cancer-related death worldwide. Surgery, chemotherapy, molecular targeted therapy, immunotherapy, and radiotherapy are currently available as treatment methods. However, drug resistance is a significant factor in the failure of lung cancer treatments. Novel therapeutics have been exploited to address complicated resistance mechanisms of lung cancer and the advancement of nanomedicine is extremely promising in terms of overcoming drug resistance. Nanomedicine equipped with multifunctional and tunable physiochemical properties in alignment with tumor genetic profiles can achieve precise, safe, and effective treatment while minimizing or eradicating drug resistance in cancer. Here, this work reviews the discovered resistance mechanisms for lung cancer chemotherapy, molecular targeted therapy, immunotherapy, and radiotherapy, and outlines novel strategies for the development of nanomedicine against drug resistance. This work focuses on engineering design, customized delivery, current challenges, and clinical translation of nanomedicine in the application of resistant lung cancer.

Recent Uses of Lipid Nanoparticles, Cell-Penetrating and Bioactive Peptides for the Development of Brain-Targeted Nanomedicines against Neurodegenerative Disorders

The lack of effective treatments for neurodegenerative diseases (NDs) is an important current concern. Lipid nanoparticles can deliver innovative combinations of active molecules to target the various mechanisms of neurodegeneration. A significant challenge in delivering drugs to the brain for ND treatment is associated with the blood–brain barrier, which limits the effectiveness of conventional drug administration. Current strategies utilizing lipid nanoparticles and cell-penetrating peptides, characterized by various uptake mechanisms, have the potential to extend the residence time and bioavailability of encapsulated drugs. Additionally, bioactive molecules with neurotropic or neuroprotective properties can be delivered to potentially mediate the ND targeting pathways, e.g., neurotrophin deficiency, impaired lipid metabolism, mitochondrial dysfunction, endoplasmic reticulum stress, accumulation of misfolded proteins or peptide fragments, toxic protein aggregates, oxidative stress damage, and neuroinflammation. This review discusses recent advancements in lipid nanoparticles and CPPs in view of the integration of these two approaches into nanomedicine development and dual-targeted nanoparticulate systems for brain delivery in neurodegenerative disorders.

Nanomedicine approaches against SARS-CoV-2 and variants

The world is grappling with the ongoing crisis of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a global pandemic that continues to have a detrimental impact on public health and economies worldwide. The virus's relentless mutation has led to more transmissible, immune-evasive strains, thereby escalating the incidence of reinfection. This underscores the urgent need for highly effective and safe countermeasures against SARS-CoV-2 and its evolving variants. In the current context, nanomedicine presents an innovative and promising alternative to mitigate the impacts of this pandemic wave. It does so by harnessing the structural and functional properties at a nanoscale in a straightforward and adaptable manner. This review emphasizes the most recent progress in the development of nanovaccines, nanodecoys, and nanodisinfectants to tackle SARS-CoV-2 and its variants. Notably, the insights gained and strategies implemented in managing the ongoing pandemic may also offer invaluable guidance for the development of potent nanomedicines to combat future pandemics.

Biomimetic theranostic nanoparticles for effective anticancer therapy and MRI imaging

Cancer remains a leading cause of mortality worldwide, necessitating the development of innovative therapeutic approaches. Nanoparticle-based drug delivery systems have garnered significant interest due to their multifunctionality, offering the potential to enhance cancer treatment efficacy and improve patient tolerability. Membrane-coated drug delivery systems hold great potential for enhancing the therapeutic outcome of nanoparticle-based anticancer therapies. In this study, we report the synthesis of multifunctional iron-functionalized mesoporous polydopamine nanoparticles (MPDAFe NPs). These nanoformulations demonstrate substantial potential for combining efficient drug delivery and magnetic resonance imaging (MRI) and showcase the advantages of biomimetic coating with tumor cell-derived membranes. This coating confers prolonged circulation and improved the targeting capabilities of the nanoparticles. Furthermore, comprehensive biosafety evaluations reveal negligible toxicity to normal cells, while the combined chemo- and phototherapy exhibited significant cytotoxicity towards cancer cells. Additionally, the photothermal effect evaluation highlights the enhanced cytotoxicity achieved through laser irradiation, showcasing the synergistic effects of the nanomaterials and photothermal therapy. Importantly, our chemotherapeutic effect evaluation demonstrates the superior efficacy of doxorubicin-loaded MPDAFe@Mem NPs (cancer cell membrane-coated MPDAFe NPs) in inhibiting cancer cell viability and proliferation, surpassing the potency of free doxorubicin. This study comprehensively investigates theranostic, membrane-coated drug delivery systems, underlining their potential to increase the efficacy of cancer treatment strategies. The multifunctional nature of the iron-functionalized polydopamine nanoparticles allows for efficient drug delivery and imaging capabilities, while the biomimetic coating enhances their biocompatibility and targeting ability. These findings contribute valuable insights towards the development of advanced nanomedicine for improved cancer therapeutics.

Nanomedicine and regulatory science: the challenges in Africa

The integrated approach in the development of nanotechnology is allowing its introduction into multiple fields, including pharmaceutical research, in which there are now several medicines containing nanomaterials or at least making nano-based claims. As a result of increasing research in nanotechnology, pre-existing medicines have been reformulated, and new medicines have been developed. This has brought challenges to the current regulatory frameworks in Europe and the United States. These regulatory agencies are known to be stringent because they have both the human capacity and skills and conducive policies and the landscape to manage new technology, unlike the agencies in most African countries. Because the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) have embraced regulatory science (RS) as a means of proactive analysis of regulatory principles, those agencies will be able to address nanomedicine challenges in a straightforward manner. African countries currently do not have a harmonized regulatory framework because different national regulatory authorities are at different levels of development. The pharmaceutical sector in Africa is facing many challenges, including the non-existence of research and development partnerships between industry, universities, and research institutions that foster nanomedicine development. Now that the African Medicine Agency (AMA) is in place, Africa should see the rapid implementation of the AU Model Law on Medical Products Regulation that will assist in putting in place capacity-building programs in nanomedicine RS.

PH-responsive star-shaped poly (ε-carprolactone)-co-poly maleic anhydride micelles for synergistic breast cancer combination chemotherapy

Polymeric micelles produced from amphiphilic copolymers, are considered promising drug delivery platforms. Because of their ability to co-deliver hydrophilic (Dox) and hydrophobic (natural sesquiterpene coumarin, Conf) drugs through their shell and core, these nanosized micelles can benefit adjuvant therapy by modulating MDR proteins and increasing cellular uptake. In this study, a novel star-shaped biodegradable pH-sensitive pentaerythritol-grafted anhydride maleic copolymerized with Poly(ε-caprolactone) (PEE-g-PMA-co-PCL) was synthesized and developed as micellar nano-carriers for combination therapy of MDA-MB-231 breast cancer cell line. The physicochemical, characteristics of the synthesized copolymers and micelles were validated using Nuclear Magnetic Resonance Spectroscopy (NMR), Fourier Transform Infrared Spectroscopy (FTIR), CHNS elemental analysis, Dynamic Light Scattering (DLS), Zeta potential, Scanning Electron Microscopy (SEM), and Differential Scanning Calorimetry (DSC). The engineered micelles exhibited nearly 100% encapsulation efficiency for both Dox and Conf. Micelles possess a CMC value of 0.1 μg/mL, an average size of 40.3 nm with uniform distribution; ζ-potential of −11.5 mV in blank form and + 6.82 mV in co-drug-loaded form. Furthermore, micelles' in vitro biodegradation and drug release profiles followed an intensive pH-dependent pattern that benefited targeted delivery. The results of MTT, cellular uptake, cell cycle, and apoptosis by Annexin V assay on MDA-MB-231 cell line cells treated by co-drug loaded micelles (E2D) demonstrated higher cytotoxicity, more cellular uptake, superior inhibitory yield on DNA duplication, and greater apoptosis with a lower necrosis rate compared to monotherapy (ED and EC) and free drugs (Conf, Dox and 2D) which confirmed the synergistic effect of this combination therapy system (CI < 1) in a reduced Dox dosage. In addition, western blot and RT-PCR showed that co-drug-loaded micelles triggered an apoptotic response via the mitochondrial pathway. In conclusion, the novel developed multi-functional pH-sensitive micelles here could open a new perspective for the development of nanomedicine for combination chemo-adjuvant therapy against malignant cancer.

Disturbing cytoskeleton by engineered nanomaterials for enhanced cancer therapeutics.

Cytoskeleton plays a significant role in the shape change, migration, movement, adhesion, cytokinesis, and phagocytosis of tumor cells. In clinical practice, some anti-cancer drugs achieve cytoskeletal therapeutic effects by acting on different cytoskeletal protein components. However, in the absence of cell-specific targeting, unnecessary cytoskeletal recombination in organisms would be disastrous, which would also bring about severe side effects during anticancer process. Nanomedicine have been proven to be superior to some small molecule drugs in cancer treatment due to better stability and targeting, and lower side effects. Therefore, this review summarized the recent developments of various nanomaterials disturbing cytoskeleton for enhanced cancer therapeutics, including carbon, noble metals, metal oxides, black phosphorus, calcium, silicon, polymers, peptides, and metal-organic frameworks, etc. A comprehensive analysis of the characteristics of cytoskeleton therapy as well as the future prospects and challenges towards clinical application were also discussed. We aim to drive on this emerging topic through refreshing perspectives based on our own work and what we have also learnt from others. This review will help researchers quickly understand relevant cytoskeletal therapeutic information to further advance the development of cancer nanomedicine.

ROS-based nanomedicines for anti-inflammatory therapies

Graphical abstract Abstract Reactive oxygen species (ROS) are important signaling molecules that play key roles in the progression of inflammatory disorders. Owing to a mismatch of the antioxidant level to balance the overproduction of ROS, the induced chronic inflammation can lead to several type of diseases such as cancer, inflammatory bowel disease, atherosclerosis, diabetes or neurodegenerative disorders. Over the last years, nanomedicine has shown tremendous promise in ROS-regulating approaches. The development of advanced redox-active nanomaterials opened the range of possibilities to anti-inflammatory therapies, with the production of ROS-responsive nanosystems enabling targeted drug delivery or with the manufacture of ROS-scavenging nanomaterials reducing ROS excess levels. This review summarizes the latest developments and novel designs of ROS-based nanomedicines and discusses their therapeutical strategies and applications.

Recent Progress in Phage-Based Nanoplatforms for Tumor Therapy.

Nanodrug delivery systems have demonstrated a great potential for tumor therapy with the development of nanotechnology. Nonetheless, traditional drug delivery systems are faced with issues such as complex synthetic procedures, low reproducibility, nonspecific distribution, impenetrability of biological barrier, systemic toxicity, etc. In recent years, phage-based nanoplatforms have attracted increasing attention in tumor treatment for their regular structure, fantastic carrying property, high transduction efficiency and biosafety. Notably, therapeutic or targeting peptides can be expressed on the surface of the phages through phage display technology, enabling the phage vectors to possess multifunctions. As a result, the drug delivery efficiency on tumor will be vastly improved, thereby enhancing the therapeutic efficacy while reducing the side effects on normal tissues. Moreover, phages can overcome the hindrance of biofilm barrier to elicit antitumor effects, which exhibit great advantages compared with traditional synthetic drug delivery systems. Herein, this review not only summarizes the structure and biology of the phages, but also presents their potential as prominent nanoplatforms against tumor in different pathways to inspire the development of effective nanomedicine.

MiRNAs involvement in the etiology and targeted therapy of bladder cancer: Interaction between signaling pathway

AbstractBladder cancer (BC) accounts for roughly 3% of all cancer diagnoses in developed countries. The prognosis could be improved significantly if the cancer is detected and classified as either muscle‐invasive bladder cancer (MIBC) or non‐muscle‐invasive bladder cancer (NMIBC) as promptly as possible. A potential ray of hope for the treatment of BC has emerged with the rapid development of nanomedicine and microRNAs (miRNAs), which promise to have fewer adverse effects, more tumor‐inhibitory effects, and decreased drug resistance. The complex interplay between hereditary and environmental variables is the root cause of this malignancy. Gene expression can be regulated by miRNAs, which are small, non‐coding RNAs that can either prevent the translation of protein‐coding genes or cleave RNA transcripts at certain locations. Elevated genomics has enabled a more extensive investigation of miRNAs whose expression is considerably different in BC patients compared to healthy volunteers or between BC tumor tissues and peripheral tissues. miRNAs have recently been discovered to be important regulators of BC cell carcinogenicity. Inaccurate diagnoses and prolonged treatment delays are more likely to occur due to the current diagnostic process such as lack of sensitivity and specificity and poor image quality. Patients now have access to a plethora of treatment options, including but not limited to surgery, chemotherapy, immunotherapy, gene therapy, and other innovative medicines, and in some cases, combination therapies. BC is one of the deadliest and most disabling malignancies affecting the urinary tract. Cancer of the urinary bladder has a terrible propensity for being fatal. BC is an intricate illness whose development can be affected by multiple parameters. Standard treatments for BC increase prognosis and survival, although recurrence is a major concern for patients. miRNAs are naturally occurring, small RNA molecules that have been linked to cancer through their expression being dysregulated. miRNAs modulate many cellular activities including proliferation, migration, differentiation, and apoptosis. MiRNA dysregulation is recognized in BC, and miRNAs are used as diagnostic and prognostic indicators. However, this manuscript discusses the recent progress made in nanomedicine and the function of miRNAs in the pathogenesis and targeted therapy of BC.

Nano-Bio Interactions: Biofilm-Targeted Antibacterial Nanomaterials.

Biofilm is a spatially organized community formed by the accumulation of both microorganisms and their secretions, leading to persistent and chronic infections because of high resistance toward conventional antibiotics. In view of the tunable physicochemical properties and the related unique biological behavior (e.g., size-, shape-, and surface charge-dependent penetration, protein corona endowed targeting, catalytic- and electronic-related oxidative stress, optical- and magnetic-associated hyperthermia, etc.), nanomaterials-based therapeutics are widely used for the treatment of biofilm-associated infections. In this review, the biological characteristics of biofilm are introduced. And the nanomaterials-based antibacterial strategies are further discussed via biofilm targeting, including preventing biofilm formation, enhancing biofilm penetration, disrupting the mature biofilm, and acting as drug delivery systems. In which, the interactions between biofilm and nanomaterials include mechanical disruption, electron transfer, enzymatic degradation, oxidative stress, and hyperthermia. Additionally, the current advances of nanomaterials for antibacterial nanomaterials by biofilm targeting are summarized. This review aims to present a complete vision of antibacterial nanomaterials-biofilm (nano-bio) interactions, paving the way for the future development and clinical translation of effective antibacterial nanomedicines.