Nanomedicine and Society

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110021/1/cptclpt2008276.pd

From design to clinic: Engineered peptide nanomaterials for cancer immunotherapy

Immunotherapy has revolutionized the field of cancer therapy. Nanomaterials can further improve the efficacy and safety of immunotherapy because of their tunability and multifunctionality. Owing to their natural biocompatibility, diverse designs, and dynamic self-assembly, peptide-based nanomaterials hold great potential as immunotherapeutic agents for many malignant cancers, with good immune response and safety. Over the past several decades, peptides have been developed as tumor antigens, effective antigen delivery carriers, and self-assembling adjuvants for cancer immunotherapy. In this review, we give a brief introduction to the use of peptide-based nanomaterials for cancer immunotherapy as antigens, carriers, and adjuvants, and to their current clinical applications. Overall, this review can facilitate further understanding of peptide-based nanomaterials for cancer immunotherapy and may pave the way for designing safe and efficient methods for future vaccines or immunotherapies

Atomic Force Microscopy Images Label-Free, Drug Encapsulated Nanoparticles In Vivo and Detects Difference in Tissue Mechanical Properties of Treated and Untreated: A Tip for Nanotoxicology

Overcoming the intractable challenge of imaging of label-free, drug encapsulated nanoparticles in tissues in vivo would directly address associated regulatory concerns over 'nanotoxicology'. Here we demonstrate the utility of Atomic Force Microscopy (AFM) for visualising label-free, drug encapsulated polyester particles of ~280 nm distributed within tissues following their intravenous or peroral administration to rodents. A surprising phenomenon, in which the tissues' mechanical stiffness was directly measured (also by AFM) and related to the number of embedded nanoparticles, was utilised to generate quantitative data sets for nanoparticles localisation. By coupling the normal determination of a drug's pharmacokinetics/pharmacodynamics with post-sacrifice measurement of nanoparticle localisation and number, we present for the first time an experimental design in which a single in vivo study relates the PK/PD of a nanomedicine to its toxicokinetics

Nanomedical Theranostics in Cardiovascular Disease

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. New diagnostic and therapeutic strategies are needed to mitigate this public health issue. Advances in nanotechnology have generated innovative strategies for diagnosis and therapy in a variety of diseases, foremost in cancer. Based on these studies, a novel concept referred to as nanomedical theranostics, or the combinatory application of nanoparticulate agents to allow diagnostic therapy, is being explored to enable image-guided, personalized, or targeted treatment. Preclinically, theranostics have been gradually applied to CVD with several interesting and encouraging findings. This article summarizes studies and challenges of nanotheranostic strategies in CVD. It also evaluates nanotheranostic strategies that may potentially be utilized to benefit patients

Reversion of pH-Induced Physiological Drug Resistance: A Novel Function of Copolymeric Nanoparticles

The extracellular pH of cancer cells is lower than the intracellular pH. Weakly basic anticancer drugs will be protonated extracellularly and display a decreased intracellular concentration. In this study, we show that copolymeric nanoparticles (NPs) are able to overcome this “pH-induced physiological drug resistance” (PIPDR) by delivering drugs to the cancer cells via endocytosis rather than passive diffussion.As a model nanoparticle, Tetradrine (Tet, Pka 7.80) was incorporated into mPEG-PCL. The effectiveness of free Tet and Tet-NPs were compared at different extracellular pHs (pH values 6.8 and 7.4, respectively) by MTT assay, morphological observation and apoptotic analysis in vitro and on a murine model by tumor volume measurement, PET-CT scanning and side effect evaluation in vivo.<0.05) when the extracellular pH decreased from 7.4 to 6.8. Meanwhile, the cytotoxicity of Tet-NPs was not significantly influenced by reduced pH. In vivo experiment also revealed that Tet-NPs reversed PIPDR more effectively than other existing methods and with much less side effects.The reversion of PIPDR is a new discovered mechanism of copolymeric NPs. This study emphasized the importance of cancer microenvironmental factors in anticancer drug resistance and revealed the superiority of nanoscale drug carrier from a different aspect

Porous Bead-Based Diagnostic Platforms: Bridging the Gaps in Healthcare

Advances in lab-on-a-chip systems have strong potential for multiplexed detection of a wide range of analytes with reduced sample and reagent volume; lower costs and shorter analysis times. The completion of high-fidelity multiplexed and multiclass assays remains a challenge for the medical microdevice field; as it struggles to achieve and expand upon at the point-of-care the quality of results that are achieved now routinely in remote laboratory settings. This review article serves to explore for the first time the key intersection of multiplexed bead-based detection systems with integrated microfluidic structures alongside porous capture elements together with biomarker validation studies. These strategically important elements are evaluated here in the context of platform generation as suitable for near-patient testing. Essential issues related to the scalability of these modular sensor ensembles are explored as are attempts to move such multiplexed and multiclass platforms into large-scale clinical trials. Recent efforts in these bead sensors have shown advantages over planar microarrays in terms of their capacity to generate multiplexed test results with shorter analysis times. Through high surface-to-volume ratios and encoding capabilities; porous bead-based ensembles; when combined with microfluidic elements; allow for high-throughput testing for enzymatic assays; general chemistries; protein; antibody and oligonucleotide applications

Nanotechnology and the Treatment of HIV Infection

Suboptimal adherence, toxicity, drug resistance and viral reservoirs make the lifelong treatment of HIV infection challenging. The emerging field of nanotechnology may play an important role in addressing these challenges by creating drugs that possess pharmacological advantages arising out of unique phenomena that occur at the “nano” scale. At these dimensions, particles have physicochemical properties that are distinct from those of bulk materials or single molecules or atoms. In this review, basic concepts and terms in nanotechnology are defined, and examples are provided of how nanopharmaceuticals such as nanocrystals, nanocapsules, nanoparticles, solid lipid nanoparticles, nanocarriers, micelles, liposomes and dendrimers have been investigated as potential anti-HIV therapies. Such drugs may, for example, be used to optimize the pharmacological characteristics of known antiretrovirals, deliver anti-HIV nucleic acids into infected cells or achieve targeted delivery of antivirals to the immune system, brain or latent reservoirs. Also, nanopharmaceuticals themselves may possess anti-HIV activity. However several hurdles remain, including toxicity, unwanted biological interactions and the difficulty and cost of large-scale synthesis of nanopharmaceuticals

Biodegradable, Drug-Loaded Nanovectors via Direct Hydration as a New Platform for Cancer Therapeutics

The stabilization and transport of low-solubility drugs, by encapsulation in nanoscopic delivery vectors (nanovectors), is a key paradigm in nanomedicine. However, the problems of carrier toxicity, specificity, and producibility create a bottleneck in the development of new nanomedical technologies. Copolymeric nanoparticles are an excellent platform for nanovector engineering due to their structural versatility; however, conventional fabrication processes rely upon harmful chemicals that necessitate purification. In engineering a more robust (copolymeric) nanovector platform, it is necessary to reconsider the entire process from copolymer synthesis through self-assembly and functionalization. To this end, a process is developed whereby biodegradable copolymers of poly(ethylene glycol)-block-poly(trimethylene carbonate), synthesized via organocatalyzed ring-opening polymerization, undergo assembly into highly uniform, drug-loaded micelles without the use of harmful solvents or the need for purification. The direct hydration methodology, employing oligo(ethylene glycol) as a nontoxic dispersant, facilitates rapid preparation of pristine, drug-loaded nanovectors that require no further processing. This method is robust, fast, and scalable. Utilizing parthenolide, an exciting candidate for treatment of acute lymphoblastic leukemia (ALL), discrete nanovectors are generated that show strikingly low carrier toxicity and high levels of specific therapeutic efficacy against primary ALL cells (as compared to normal hematopoietic cells)