recent developments in cancer nanomedicine

Since decades, conventional diagnosis and treatment strategies for cancer have been practiced widely despite their expensive and time-consuming process. These conventional contrast and therapeutic agents suffer from various side-effects such as low radiodensity and image resolution, rapid clearance, non-specific biodistribution, poor tumor accumulation, high-dose and multiple-dose requirements, nephrotoxicity, uncontrolled exposure of high electromagnetic radiations, whole-body scans, and so on. Therefore, nanosized imaging and therapeutic probes have been proposed recently owing to their promising efficacy and negligible side-effects. However, these nanoplatforms are struggling deeply to find their clinical translational relevance. Integrating targeting ligands with diagnostic and therapeutic agents within a single system at the nanoscale resulted in localized nanotheranostics. Furthermore, the conceptualized nanotheranostics has been recognized as a clinical ‘weapon’ for localized cancer nanomedicine. In this review, we have covered a wide spectrum of recent developments in cancer nanotheranostics. Numerous examples of functional nanohybrids and clinical relevant materials with their multimode imaging and therapeutics have been addressed here. On the other hand, the importance of combination therapies, imaging-guided tumor regression, deep tissue visualization, localized diagnosis and tumor ablation, manipulation of the tumor microenvironment, and so on have been discussed here. Overall, localized and stimuli responsive nanosized multifunctional platforms have proved their superiority over conventional diagnosis and therapies.publishersversionpublishe

Current Trends in Cancer Nanotheranostics: Metallic, Polymeric, and Lipid-Based Systems

Theranostics has emerged in recent years to provide an efficient and safer alternative in cancer management. This review presents an updated description of nanotheranostic formulations under development for skin cancer (including melanoma), head and neck, thyroid, breast, gynecologic, prostate, and colon cancers, brain-related cancer, and hepatocellular carcinoma. With this focus, we appraised the clinical advantages and drawbacks of metallic, polymeric, and lipid-based nanosystems, such as low invasiveness, low toxicity to the surrounding healthy tissues, high precision, deeper tissue penetration, and dosage adjustment in a real-time setting. Particularly recognizing the increased complexity and multimodality in this area, multifunctional hybrid nanoparticles, comprising different nanomaterials and functionalized with targeting moieties and/or anticancer drugs, present the best characteristics for theranostics. Several examples, focusing on their design, composition, imaging and treatment modalities, and in vitro and in vivo characterization, are detailed herein. Briefly, all studies followed a common trend in the design of these theranostics modalities, such as the use of materials and/or drugs that share both inherent imaging (e.g., contrast agents) and therapeutic properties (e.g., heating or production reactive oxygen species). This rationale allows one to apparently overcome the heterogeneity, complexity, and harsh conditions of tumor microenvironments, leading to the development of successful targeted therapies.The authors acknowledge Fundação para a Ciência e a Tecnologia (FCT) for financial support through Projects UID/DTP/04138/2013, PTDC/MED-QUI/31721/2017 and for financial support through PhD fellowship SFRH/BD/117586/2016.info:eu-repo/semantics/publishedVersio

Gold nanoparticles enlighten the future of cancer theranostics

Development of multifunctional nanomaterials, one of the most interesting and advanced research areas in the field of nanotechnology, is anticipated to revolutionize cancer diagnosis and treatment. Gold nanoparticles (AuNPs) are now being widely utilized in bioimaging and phototherapy due to their tunable and highly sensitive optical and electronic properties (the surface plasmon resonance). As a new concept, termed “theranostics,” multifunctional AuNPs may contain diagnostic and therapeutic functions that can be integrated into one system, thereby simultaneously facilitating diagnosis and therapy and monitoring therapeutic responses. In this review, the important properties of AuNPs relevant to diagnostic and phototherapeutic applications such as structure, shape, optics, and surface chemistry are described. Barriers for translational development of theranostic AuNPs and recent advances in the application of AuNPs for cancer diagnosis, photothermal, and photodynamic therapy are discussed

Nanomedicine-driven molecular targeting, drug delivery, and therapeutic approaches to cancer chemoresistance

Cancer cell resistance to chemotherapeutics (chemoresistance) poses a significant clinical challenge that oncology research seeks to understand and overcome. Multiple anticancer drugs and targeting agents can be incorporated in nanomedicines, in addition to different treatment modalities, forming a single nanoplatform that can be used to address tumor chemoresistance. Nanomedicine-driven molecular assemblies using nucleic acids, small interfering (si)RNAs, miRNAs, and aptamers in combination with stimuli-responsive therapy improve the pharmacokinetic (PK) profile of the drugs and enhance their accumulation in tumors and, thus, therapeutic outcomes. In this review, we highlight nanomedicine-driven molecular targeting and therapy combination used to improve the 3Rs (right place, right time, and right dose) for chemoresistant tumor therapies

Doctor of Philosophy

dissertationTreatment of cancer is a significant challenge due to the heterogeneity of both tumors and patients. This realization has led to the field of personalized medicine in which patients can be selected for a therapy based on the specific needs. One potential area for personalized medicine is utilizing medical imaging to predict and monitor the therapeutic efficacy and safety of a particular targeted therapy. Development of image- guided therapeutics based on macromolecular carriers such as N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers is advantageous because they are water-soluble and can contain a wide range of comonomers to confer multifunctionality. HPMA copolymers are water-soluble nano-sized constructs which can improve the delivery of therapeutics to tumors by passive targeting via the enhanced permeability and retention effect. They can also increase tumor uptake using targeting ligands that are conjugated to the backbone of the copolymer. This dissertation focuses on the development of targeted HPMA copolymers for delivery of both therapeutics and imaging agents to solid tumors. Barriers to delivery of these constructs were addressed in various tumor models. In pancreatic tumors, the desmoplastic response, or dense extracellular matrix prevents delivery of drugs and macromolecules alike. Treating hyaluronic acid, a component of desmoplasia, with hyaluronidase allowed for increased delivery of HPMA copolymers based on HER2 and αvβ3 integrin targeting strategies for HPMA copolymers. Based on the selection of HER2 as a viable tumor targeting strategy, iv an image-guided drug delivery (IGDD) system was synthesized, characterized and evaluated in vitro in pancreatic tumor cell lines. In vitro results suggest that the designed construct was potentially capable of targeting, binding, treating and imaging pancreatic tumors for an IGDD approach. Lastly, a study was conducted in a prostate tumor model for localized tumor delivery of a 90Y radiolabeled HPMA copolymers for radiotherapy. Imaging tumor localization and biodistribution was accomplished using an equivalent 111In radiolabeled HPMA copolymer. Targeting and efficacy were accomplished via gold nanorod (GNR)-mediated hyperthermia and demonstrated antitumor efficacy in the prostate tumor mouse model. The combined studies demonstrate the current progress for development of an HPMA copolymer conjugate for image-guided therapy of solid tumors

New Approaches to Photodynamic Therapy from Type I, II and III to Type IV Using One or More Photons

Photodynamic therapy (PDT) is an alternative cancer treatment to conventional surgery, radiotherapy and chemotherapy. It is based on activating a drug with light that triggers the generation of cytotoxic species that promote tumour cell killing. At present, PDT is mainly used in the treatment of wet age-related macular degeneration, for precancerous conditions of the skin (e.g. actinic keratosis) and in the palliative care of advanced cancers, for instance of the bladder or the oesophagus. PDT is still not used as a first line cancer treatment, which is surprising given the first clinical trials by Dougherty’s group dating back to the 1970’s. PDT has significant advantages over surgery or radiation therapy for low lying tumours due to better cosmetic outcome and localised treatment for the patients. However, despite these advantages and significant developments in optical technology that has enabled light penetration to deeper lying tumours, in excess of 5 cm, a lack of phase III clinical trials has slowed down the uptake of PDT by the healthcare sector as a frontline treatment in cancer. However research continues to demonstrate the potential benefits of PDT and the need to stimulate funding and uptake of clinical studies using next generation photosensitizers offering advanced targeted delivery, improved photodynamic dose combined with modern light delivery technologies. This review surveys the available PDT treatments and emerging novel developments in the field with a particular focus on two-photon techniques that are anticipated to improve the effectiveness of PDT in tissues at depth and on next generation drugs that work without the need of the presence of oxygen for photosensitization making them effective where hypoxia has taken hold