Image-guided drug delivery of nanotheranostics for targeted lung cancer therapy.
Ontology highlight
ABSTRACT:
SUBMITTER: Yin X
PROVIDER: S-EPMC9169367 | biostudies-literature | 2022
REPOSITORIES: biostudies-literature
Publications
Image-guided drug delivery of nanotheranostics for targeted lung cancer therapy.
Yin Xiaoran X Cui Yanan Y Kim Richard S RS Stiles Wesley R WR Park Seung Hun SH Wang Haoran H Ma Li L Chen Lin L Baek Yoonji Y Kashiwagi Satoshi S Bao Kai K Ulumben Amy A Fukuda Takeshi T Kang Homan H Choi Hak Soo HS
Theranostics 20220513 9
Enormous efforts have been made to integrate various therapeutic interventions into multifunctional nanoplatforms, resulting in the advance of nanomedicine. Image-guided drug delivery plays a pivotal role in this field by providing specific targeting as well as image navigation for disease prognosis. <b>Methods:</b> We demonstrate image-guided surgery and drug delivery for the treatment of lung cancer using nanotheranostic H-dots loaded with gefitinib and genistein. <b>Results:</b> The surgical ...[more]
Similar Datasets
Project description:Cancer heterogeneity and drug resistance limit the efficacy of cancer therapy. To address this issue, we have developed an integrated treatment protocol for effective treatment of heterogeneous ovarian cancer. Methods: An amphiphilic polymer coated magnetic iron oxide nanoparticle was conjugated with near infrared dye labeled HER2 affibody and chemotherapy drug cisplatin. The effects of the theranostic nanoparticle on targeted drug delivery, therapeutic efficacy, non-invasive magnetic resonance image (MRI)-guided therapy, and optical imaging detection of therapy resistant tumors were examined in an orthotopic human ovarian cancer xenograft model with highly heterogeneous levels of HER2 expression. Results: We found that systemic delivery of HER2-targeted magnetic iron oxide nanoparticles carrying cisplatin significantly inhibited the growth of primary tumor and peritoneal and lung metastases in the ovarian cancer xenograft model in nude mice. Differential delivery of theranostic nanoparticles into individual tumors with heterogeneous levels of HER2 expression and various responses to therapy were detectable by MRI. We further found a stronger therapeutic response in metastatic tumors compared to primary tumors, likely due to a higher level of HER2 expression and a larger number of proliferating cells in metastatic tumor cells. Relatively long-time retention of iron oxide nanoparticles in tumor tissues allowed interrogating the relationship between nanoparticle drug delivery and the presence of resistant residual tumors by in vivo molecular imaging and histological analysis of the tumor tissues. Following therapy, most of the remaining tumors were small, primary tumors that had low levels of HER2 expression and nanoparticle drug accumulation, thereby explaining their lack of therapeutic response. However, a few residual tumors had HER2-expressing tumor cells and detectable nanoparticle drug delivery but failed to respond, suggesting additional intrinsic resistant mechanisms. Nanoparticle retention in the small residual tumors, nevertheless, produced optical signals for detection by spectroscopic imaging. Conclusion: The inability to completely excise peritoneal metastatic tumors by debulking surgery as well as resistance to chemotherapy are the major clinical challenges for ovarian cancer treatment. This targeted cancer therapy has the potential for the development of effective treatment for metastatic ovarian cancer.
| S-EPMC6376473 | biostudies-literature
Project description:Image-guided nanotheranostics have the potential to represent a new paradigm in the treatment of cancer. Recent developments in modern imaging and nanoparticle design offer an answer to many of the issues associated with conventional chemotherapy, including their indiscriminate side effects and susceptibility to drug resistance. Imaging is one of the tools best poised to enable tailoring of cancer therapies. The field of image-guided nanotheranostics has the potential to harness the precision of modern imaging techniques and use this to direct, dictate, and follow site-specific drug delivery, all of which can be used to further tailor cancer therapies on both the individual and population level. The use of image-guided drug delivery has exploded in preclinical and clinical trials although the clinical translation is incipient. This review will focus on traditional mechanisms of targeted drug delivery in cancer, including the use of molecular targeting, as well as the foundations of designing nanotheranostics, with a focus on current clinical applications of nanotheranostics in cancer. A variety of specially engineered and targeted drug carriers, along with strategies of labeling nanoparticles to endow detectability in different imaging modalities will be reviewed. It will also introduce newer concepts of image-guided drug delivery, which may circumvent many of the issues seen with other techniques. Finally, we will review the current barriers to clinical translation of image-guided nanotheranostics and how these may be overcome.
| S-EPMC9144228 | biostudies-literature
Project description:Nanomedicine involves the use of nanotechnology for clinical applications and holds promise to improve treatments. Recent developments offer new hope for cancer detection, prevention and treatment; however, being a heterogenous disorder, cancer calls for a more targeted treatment approach. Personalized Medicine (PM) aims to revolutionize cancer therapy by matching the most effective treatment to individual patients. Nanotheranostics comprise a combination of therapy and diagnostic imaging incorporated in a nanosystem and are developed to fulfill the promise of PM by helping in the selection of treatments, the objective monitoring of response and the planning of follow-up therapy. Although well-established imaging techniques, such as Magnetic Resonance Imaging (MRI), Computed Tomography (CT), Positron Emission Tomography (PET) and Single-Photon Emission Computed Tomography (SPECT), are primarily used in the development of theranostics, Optical Imaging (OI) offers some advantages, such as high sensitivity, spatial and temporal resolution and less invasiveness. Additionally, it allows for multiplexing, using multi-color imaging and DNA barcoding, which further aids in the development of personalized treatments. Recent advances have also given rise to techniques permitting better penetration, opening new doors for OI-guided nanotheranostics. In this review, we describe in detail these recent advances that may be used to design and develop efficient and specific nanotheranostics for personalized cancer drug delivery.
| S-EPMC8838478 | biostudies-literature
Project description:Lung cancer (LC) is often diagnosed at an advanced stage and conventional treatments for disease management have limitations associated with them. Novel therapeutic targets are thus avidly sought for the effective management of LC. RNA binding proteins (RBPs) have been convincingly established as key players in tumorigenesis, and their dysregulation is linked to multiple cancers, including LC. In this context, we review the role of Human antigen R (HuR), an RBP that is overexpressed in LC, and further associated with various aspects of LC tumor growth and response to therapy. Herein, we describe the role of HuR in LC progression and outline the evidences supporting various pharmacologic and biologic approaches for inhibiting HuR expression and function. These approaches, including use of small molecule inhibitors, siRNAs and shRNAs, have demonstrated favorable results in reducing tumor cell growth, invasion and migration, angiogenesis and metastasis. Hence, HuR has significant potential as a key therapeutic target in LC. Use of siRNA-based approaches, however, have certain limitations that prevent their maximal exploitation as cancer therapies. To address this, in the conclusion of this review, we provide a list of nanomedicine-based HuR targeting approaches currently being employed for siRNA and shRNA delivery, and provide a rationale for the immense potential therapeutic benefits offered by nanocarrier-based HuR targeting and its promise for treating patients with LC.
| S-EPMC8724414 | biostudies-literature
Project description:On April 17, 2010, scientists from academia, the National Cancer Institute (NCI), and the Food and Drug Administration (FDA) assembled at "The NCI Image Guided Drug Delivery Summit," in Washington D.C., to discuss recent advances, barriers, opportunities, and regulatory issues related to the field. The meeting included a scientific session and an NCI/FDA session, followed by a panel discussion of speakers from both sessions. Image-guided drug delivery (IGDD) in cancer is a form of individualized therapy where imaging methods are used in guidance and monitoring of localized and targeted delivery of therapeutics to the tumor. So, a systematic approach to IGDD requires mechanisms for targeting, delivery, activation, and monitoring of the process. Although the goal in IGDD is to optimize the therapeutic ratio through personalized image-guided treatments, a major challenge is in overcoming the biological barriers to the delivery of therapeutics into tumors and cells. Speakers discussed potential challenges to clinical translation of nano-based drug delivery systems including in vivo characterization of nanocarriers, preclinical validation of targeting and delivery, studies of biodistribution, pharmacokinetics, pharmacodynamics, and toxicity as well as scale-up manufacturing of delivery systems. Physiologic and quantitative imaging techniques may serve as enabling tools that could potentially transform many existing challenges into opportunities for advancement of the field.
| S-EPMC3075539 | biostudies-literature
Project description:The ability to destroy cancer cells while sparing normal tissue is highly sought after in cancer therapy. Small interfering RNA (siRNA)-mediated silencing of cancer-cell-specific targets and the use of a prodrug enzyme delivered to the tumor to convert a nontoxic prodrug to an active drug are two promising approaches in achieving this goal. Combining both approaches into a single treatment strategy can amplify selective targeting of cancer cells while sparing normal tissue. Noninvasive imaging can assist in optimizing such a strategy by determining effective tumor delivery of the siRNA and prodrug enzyme to time prodrug administration and detecting target down-regulation by siRNA and prodrug conversion by the enzyme. In proof-of-principle studies, we synthesized a nanoplex carrying magnetic resonance imaging (MRI) reporters for in vivo detection and optical reporters for microscopy to image the delivery of siRNA and a functional prodrug enzyme in breast tumors and achieve image-guided molecular targeted cancer therapy. siRNA targeting of choline kinase-α (Chk-α), an enzyme significantly up-regulated in aggressive breast cancer cells, was combined with the prodrug enzyme bacterial cytosine deaminase (bCD) that converts the nontoxic prodrug 5-fluorocytosine (5-FC) to cytotoxic 5-fluorouracil (5-FU). In vivo MRI and optical imaging showed efficient intratumoral nanoplex delivery. siRNA-mediated down-regulation of Chk-α and the conversion of 5-FC to 5-FU by bCD were detected noninvasively with (1)H MR spectroscopic imaging and (19)F MR spectroscopy. Combined siRNA and prodrug enzyme activated treatment achieved higher growth delay than either treatment alone. The strategy can be expanded to target multiple pathways with siRNA.
| S-EPMC2991391 | biostudies-literature
Project description:BackgroundLung cancer is one of the most frequent causes of cancer-related deaths worldwide. Drug repurposing and nano-drug delivery systems are attracting considerable attention for improving anti-cancer therapy. Sertaconazole (STZ), an antifungal agent, has been reported to exhibit cytotoxicity against both normal and tumor cells, and its medical use is limited by its poor solubility. In order to overcome such shortcomings, we prepared a drug-repurposed nanoplatform to enhance the anti-tumor efficiency.MethodsNanoplatform was prepared by thin film dispersion. Drug release studies and uptake studies were measured in vitro. Subsequently, we verified the tumor inhibition mechanisms of HTS NPs through apoptosis assay, immunoblotting and reactive oxygen species (ROS) detection analyses. Antitumor activity was evaluated on an established xenograft lung cancer model in vivo.ResultsOur nanoplatform improved the solubility of sertaconazole and increased its accumulation in tumor cells. Mechanistically, HTS NPs was dependent on ROS-mediated apoptosis and pro-apoptotic autophagy to achieve their excellent anti-tumor effects. Furthermore, HTS NPs also showed strong inhibitory ability in nude mouse xenograft models without significant side effects.ConclusionsOur results suggest that sertaconazole-repurposed nanoplatform provides an effective strategy for lung cancer treatment.
| S-EPMC10385912 | biostudies-literature
Project description:Overcoming resistance to chemotherapy is a major and unmet medical challenge in the treatment of pancreatic cancer. Poor drug delivery due to stromal barriers in the tumor microenvironment and aggressive tumor biology are additional impediments toward a more successful treatment of pancreatic cancer. In attempts to address these challenges, we developed IGF1 receptor (IGF1R)-directed, multifunctional theranostic nanoparticles for targeted delivery of therapeutic agents into IGF1R-expressing drug-resistant tumor cells and tumor-associated stromal cells. These nanoparticles were prepared by conjugating recombinant human IGF1 to magnetic iron oxide nanoparticles (IONPs) carrying the anthracycline doxorubicin (Dox) as the chemotherapeutic payload. Intravenously administered IGF1-IONPs exhibited excellent tumor targeting and penetration in an orthotopic patient-derived xenograft (PDX) model of pancreatic cancer featuring enriched tumor stroma and heterogeneous cancer cells. IGF1R-targeted therapy using the theranostic IGF1-IONP-Dox significantly inhibited the growth of pancreatic PDX tumors. The effects of the intratumoral nanoparticle delivery and therapeutic responses in the orthotopic pancreatic PDX tumors could be detected by magnetic resonance imaging (MRI) with IONP-induced contrasts. Histological analysis showed that IGF1R-targeted delivery of Dox significantly inhibited cell proliferation and induced apoptotic cell death of pancreatic cancer cells. Therefore, further development of IGF1R-targeted theranostic IONPs and MRI-guided cancer therapy as a precision nanomedicine may provide the basis for more effective treatment of pancreatic cancer.
| S-EPMC4908958 | biostudies-literature
Project description:It has been seventy years since a water-soluble version of vitamin E called tocophersolan (also known as TPGS) was produced; it was approved by USFDA in 1998 as an inactive ingredient. Drug formulation developers were initially intrigued by its surfactant qualities, and gradually it made its way into the toolkit of pharmaceutical drug delivery. Since then, four drugs with TPGS in their formulation have been approved for sale in the United States and Europe including ibuprofen, tipranavir, amprenavir, and tocophersolan. Improvement and implementation of novel diagnostic and therapeutic techniques for disease are goals of nanomedicine and the succeeding field of nanotheranostics. Specifically, imaging and treating tumors with nanohybrid theranostics shows promising potential. Docetaxel, paclitaxel, and doxorubicin are examples of poorly bioavailable therapeutic agents; hence, much effort is applied for developing TPGS-based nanomedicine, nanotheranostics, and targeted drug delivery systems to increase circulation time and promote the reticular endothelial escape of these drug delivery systems. TPGS has been used in a number of ways for improving drug solubility, bioavailability improvement, and prevention of drug efflux from the targeted cells, which makes it an excellent candidate for therapeutic delivery. Through the downregulation of P-gp expression and modulation of efflux pump activity, TPGS can also mitigate multidrug resistance (MDR). Novel materials such as TPGS-based copolymers are being studied for their potential use in various diseases. In recent clinical trials, TPGS has been utilized in a huge number of Phase I, II, and III studies. Additionally, numerous TPGS-based nanomedicine and nanotheranostic applications are reported in the literature which are in their preclinical stage. However, various randomized or human clinical trials have been underway for TPGS-based drug delivery systems for multiple diseases such as pneumonia, malaria, ocular disease, keratoconus, etc. In this review, we have emphasized in detail the review of the nanotheranostics and targeted drug delivery approaches premised on TPGS. In addition, we have covered various therapeutic systems involving TPGS and its analogs with special references to its patent and clinical trials.
| S-EPMC10054265 | biostudies-literature
Project description:The major obstacles in intraperitoneal (i.p.) chemotherapy of peritoneal tumors are fast absorption of drugs into the blood circulation, local and systemic toxicities, inadequate drug penetration into large tumors, and drug resistance. Targeted theranostic nanoparticles offer an opportunity to enhance the efficacy of i.p. therapy by increasing intratumoral drug delivery to overcome resistance, mediating image-guided drug delivery, and reducing systemic toxicity. Herein we report that i.p. delivery of urokinase plasminogen activator receptor (uPAR) targeted magnetic iron oxide nanoparticles (IONPs) led to intratumoral accumulation of 17% of total injected nanoparticles in an orthotopic mouse pancreatic cancer model, which was three-fold higher compared with intravenous delivery. Targeted delivery of near infrared dye labeled IONPs into orthotopic tumors could be detected by non-invasive optical and magnetic resonance imaging. Histological analysis revealed that a high level of uPAR targeted, PEGylated IONPs efficiently penetrated into both the peripheral and central tumor areas in the primary tumor as well as peritoneal metastatic tumor. Improved theranostic IONP delivery into the tumor center was not mediated by nonspecific macrophage uptake and was independent from tumor blood vessel locations. Importantly, i.p. delivery of uPAR targeted theranostic IONPs carrying chemotherapeutics, cisplatin or doxorubicin, significantly inhibited the growth of pancreatic tumors without apparent systemic toxicity. The levels of proliferating tumor cells and tumor vessels in tumors treated with the above theranostic IONPs were also markedly decreased. The detection of strong optical signals in residual tumors following i.p. therapy suggested the feasibility of image-guided surgery to remove drug-resistant tumors. Therefore, our results support the translational development of i.p. delivery of uPAR-targeted theranostic IONPs for image-guided treatment of peritoneal tumors.
| S-EPMC5436521 | biostudies-literature