Combining the power of magnetic guidance and the biological activities of stem cells transformed into biohybrid microrobots holds great promise for the treatment of several diseases including cancer.

Successful integration of nanotechnology into the current paradigm of cancer therapy requires proper understanding of the interface between nanoparticles (NPs) and cancer cells, as well as other key components within the tumor microenvironment (TME), such as normal fibroblasts (FBs) and cancer-associated FBs (CAFs). So far, much focus has been on cancer cells, but FBs and CAFs also play a critical role: FBs suppress the tumor growth while CAFs promote it. It is not yet known how NPs interact with FBs and CAFs compared to cancer cells. Hence, our goal was to elucidate the extent of NP uptake, retention, and toxicity in cancer cells, FBs, and CAFs to further understand the fate of NPs in a real tumor-like environment. The outcome of this would guide designing of NP-based delivery systems to fully exploit the TME for a better therapeutic outcome. We used gold nanoparticles as our model NP system due to their numerous applications in cancer therapy, including radiotherapy and chemotherapy. A cervical cancer cell line, HeLa, and a triple-negative breast cancer cell line, MDA-MB-231 were chosen as cancer cell lines. For this study, a clinically feasible 0.2 nM concentration of GNPs was employed. According to our results, the cancer cells and CAFs had over 25- and 10-fold higher NP uptake per unit cell volume compared to FBs, respectively. Further, the cancer cells and CAFs had over 30% higher NP retention compared to FBs. There was no observed significant toxicity due to GNPs in all the cell lines studied. Higher uptake and retention of NPs in cancer cells and CAFs FBs is very important in promoting NP-based applications in cancer therapy. Our results show potential in modulating uptake and retention of GNPs among key components of TME, in an effort to develop NP-based strategies to suppress the tumor growth. An ideal NP-based platform would eradicate tumor cells, protect FBs, and deactivate CAFs. Therefore, this study lays a road map to exploit the TME for the advancement of "smart" nanomedicines that would constitute the next generation of cancer therapeutics.

Gold nanoparticles (AuNPs) are considered as promising agents to increase the radiosensitivity of tumor cells. However, the biological mechanisms of radiation enhancement effects of AuNPs are still not well understood. We present a multi-scale Monte Carlo simulation framework within TOPAS-nBio to investigate the increase of DNA damage due to the presence of AuNPs in mouse tumor models.

Ovarian cancer is one of the deadliest gynecological malignancies. While the overall survival of ovarian cancer patients has slightly improved in recent years in the developed world, it remains clinically challenging due to its frequent late diagnosis and the lack of reliable diagnostic and/or prognostic markers. The aim of this study was to identify potential new molecular target proteins (NMTPs) responsible for the poor outcomes. When nanoparticles (NP) are exposed to biological fluids, a protein coat, termed the protein corona (PC), forms around the NP, and the PC represents a tool to identify NMTPs. This study investigates the influence of pre-processing conditions, such as lysis conditions and serum/plasma treatment, on the PC composition and the resulting identification of NMTPs.

Much in vitro research on the applicability of gold nanoparticles (GNPs) in cancer treatment has been focused on two-dimensional (2D) monolayer models. To improve this, we explored the effect of the combination of GNPs and docetaxel (DTX) with radiotherapy (RT) in a more complex three-dimensional (3D) spheroid that can better mimic a real tumour microenvironment.

A novel treatment planning framework, the Relative Biological Effective Dose (RBED), for high Z nanoparticle (NP)-enhanced photon radiotherapy is developed and tested in silico for the medical exemplar of neoadjuvant (preoperative) breast cancer MV photon radiotherapy. Two different treatment scenarios, conventional and high Z NP enhanced, were explored with a custom Geant4 application that was developed to emulate the administration of a single 2 Gy fraction as part of a 50 Gy radiotherapy treatment plan. It was illustrated that there was less than a 1% difference in the dose deposition throughout the standard and high Z NP-doped adult female phantom. Application of the RBED framework found that the extent of possible biological response with high Z NP doping was great than expected via the dose deposition alone. It is anticipated that this framework will assist the scientific community in future high Z NP-enhanced in-silico, pre-clinical and clinical trials.

Development of biocompatible multifunctional polymeric drug carriers is crucial in modern pharmaceutics aimed to create "smart" drugs. The high potential of the PEGylated comb-like polymeric nanocarrier (PNC) in delivering both traditional and experimental drugs to tumor cells in vitro and in vivo has been demonstrated previously. In the present study, we investigated the general toxicity of polyethylene glycol (PEG) processed with both covalent and non-covalent attachments of PEG to compose a comb-like polymer that behaves like a simple chain of n monomers decorated with swollen side chains. The PNC possesses properties of a water-soluble surfactant containing methyl-terminated PEG side branches in some monomer units attached covalently to the carbon chain backbone.

In the last three decades, radiopharmaceuticals have proven their effectiveness for cancer diagnosis and therapy. In parallel, the advances in nanotechnology have fueled a plethora of applications in biology and medicine. A convergence of these disciplines has emerged more recently with the advent of nanotechnology-aided radiopharmaceuticals. Capitalizing on the unique physical and functional properties of nanoparticles, radiolabeled nanomaterials or nano-radiopharmaceuticals have the potential to enhance imaging and therapy of human diseases. This article provides an overview of various radionuclides used in diagnostic, therapeutic, and theranostic applications, radionuclide production through different techniques, conventional radionuclide delivery systems, and advancements in the delivery systems for nanomaterials. The review also provides insights into fundamental concepts necessary to improve currently available radionuclide agents and formulate new nano-radiopharmaceuticals.

Colorectal cancer is one of the prominent leading causes of fatality worldwide. Despite recent advancements within the field of cancer therapy, the cure rates and long-term survivals of patients suffering from colorectal cancer have changed little. The application of conventional chemotherapeutic agents like doxorubicin is limited by some drawbacks such as cardiotoxicity and hematotoxicity. Therefore, nanotechnology has been exploited as a promising solution to address these problems. In this study, we synthesized and compared the anticancer efficacy of doxorubicin-loaded liposomes that were surface engineered with the 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-matrix metalloproteinase-2 (MMP-2) cleavable peptide-polyethylene glycol (PEG) conjugate. The peptide linker was used to cleave in response to the upregulated MMP-2 in the tumor microenvironment, thus exposing a positive charge via PEG-deshielding and enhancing liposomal uptake by tumor cells/vasculature. Liposomal formulations were characterized in terms of size, surface charge and morphology, drug loading, release properties, cell binding and uptake, and cytotoxicity.

Lung cancer is the leading cause of cancer mortality. As a heterogeneous disease, it has different subtypes and various treatment modalities. In addition to conventional surgery, radiotherapy and chemotherapy, targeted therapy and immunotherapy have also been applied in the clinics. However, drug resistance and systemic toxicity still cannot be avoided. Based on the unique properties of nanoparticles, it provides a new idea for lung cancer therapy, especially for targeted immunotherapy. When nanoparticles are used as carriers of drugs with special physical properties, the nanodrug delivery system ensures the accuracy of targeting and the stability of drugs while increasing the permeability and the aggregation of drugs in tumor tissues, showing good anti-tumor effects. This review introduces the properties of various nanoparticles including polymer nanoparticles, liposome nanoparticles, quantum dots, dendrimers, and gold nanoparticles and their applications in tumor tissues. In addition, the specific application of nanoparticle-based drug delivery for lung cancer therapy in preclinical studies and clinical trials is discussed.

Tumor microparticles (T-MPs) are considered as a tumor vaccine candidate. Although some studies have analyzed the mechanism of T-MPs as tumor vaccine, we still lack understanding of how T-MPs stimulate a strong anti-tumor immune response. Here, we show that T-MPs induce macrophages to release a key chemotactic factor CCL2, which attracts monocytes to the vaccine injection site and enhances endocytosis of antigen. Monocytes subsequently enter the draining lymph node, and differentiate into monocyte-derived DCs (moDCs), which present tumor antigens to T lymphocytes and deliver a potent anti-tumor immune response. Mechanically, T-MPs activate the cGAS-STING signaling through DNA fragments, and then induce monocytes to upregulate the expression of IRF4, which is a key factor for monocyte differentiation into moDCs. More importantly, monocytes that have endocytosed T-MPs acquire the ability to treat tumors. Collectively, this work might provide novel vaccination strategy for the development of tumor vaccines and facilitate the application of T-MPs for clinic oncotherapy.

The vascular endothelial growth factor receptor-2 (VEGFR-2) plays an important role in melanoma development and progression. Peptide vaccines have shown great potential in cancer immunotherapy by targeting VEGFR-2 as a tumor-associated antigen and boosting the immune response against both tumor cells and tumor endothelial cells. Despite this, the low efficiency of peptide vaccines has resulted in moderate therapeutic results in the majority of studies. Enhancing the delivery of peptide vaccines using nanoliposomes is an important strategy for improving the efficacy of peptide vaccines. In this regard, we designed VEGFR-2-derived peptides restricted to both mouse MHC I and human HLA-A*02:01 using immunoinformatic tools and selected three peptides representing the highest binding affinities. The peptides were encapsulated in nanoliposomal formulations using the film method plus bath sonication and characterized for their colloidal properties.

Radiotherapy (RT) is an essential component in the treatment regimens for many cancer patients. However, the dose escalation required to improve curative results is hindered due to the normal tissue toxicity that is induced. The introduction of radiosensitizers to RT treatment is an avenue that is currently being explored to overcome this issue. By introducing radiosensitizers into tumor sites, it is possible to preferentially enhance the local dose deposited. Gold nanoparticles (GNPs) are a potential candidate that have shown great promise in increasing the radiosensitivity of cancer cells through an enhancement in DNA damage. Furthermore, docetaxel (DTX) is a chemotherapeutic agent that arrests cells in the G2/M phase of the cell cycle, the phase most sensitive to radiation damage. We hypothesized that by incorporating DTX to GNP-enhanced radiotherapy treatment, we could further improve the radiosensitization experienced by cancer cells. To assess this strategy, we analyzed the radiotherapeutic effects on monolayer cell cultures in vitro, as well as on a mice prostate xenograft model in vivo while using clinically feasible concentrations for both GNPs and DTX.

The aim of this study was to compare contrast enhancement of Magnevist® (gadopentate dimeglumine (Mag)) to that of PEGylated Magnevist®-loaded liposomal nanoparticles (Mag-Lnps) in pancreatic cancer patient-derived xenograft (PDX) mouse model via magnetic resonance imaging (MRI).

Doxorubicin-loaded hollow gold nanospheres (Dox@HAuNS) are a promising technology for simultaneous trans-arterial tumor-targeted chemotherapy delivery and thermal ablation. We evaluated the efficacy of intra-arterial delivery of Dox@HAuNS followed by photothermal ablation (PTA) in a rabbit model of liver cancer. Adult New Zealand white rabbits (N=25) were inoculated with VX2 tumors into the left lobe of the liver. The animals were then randomized to sham surgery (N=5), PTA only (N=3), Dox@HAuNS only (N=5), HAuNS + PTA (N=5), and Dox@HAuNS + PTA (N=7). Nanoparticles were delivered as an emulsion with Lipiodol (Guerbet, France) via a trans-arterial approach. Following nanoparticle delivery, PTA was performed using an 808nm fibered laser at 1.5W for 3 minutes. Thermography during PTA demonstrated a sustained elevation in tumoral temperature in both HAuNS + laser and Dox@HAuNS + laser treatment groups relative to animals that underwent laser treatment without prior nanoparticle delivery.

Neuroblastoma is the most common extracranial solid malignancy in childhood which, despite the current progress in radiotherapy and chemotherapy protocols, still has a high mortality rate in high risk tumors. Nanomedicine offers exciting and unexploited opportunities to overcome the shortcomings of conventional medicine. The photocatalytic properties of FeO core-TiO shell nanocomposites and their potential for cell specific targeting suggest that nanoconstructs produced using FeO core-TiO shell nanocomposites could be used to enhance radiation effects in neuroblastoma. In this study, we evaluated bare, metaiodobenzylguanidine (MIBG) and 3,4-Dihydroxyphenylacetic acid (DOPAC) coated FeO@TiO as potential radiosensitizers for neuroblastoma in vitro.

Nanoparticles can be used as drug carriers, contrast agents and radiosensitisers for the treatment of cancer. Nanoparticles can either passively accumulate within tumour sites, or be conjugated with targeting ligands to actively enable tumour deposition. With respect to passive accumulation, particles < 150 nm accumulate with higher efficiency within the tumour microenvironment, a consequence of the enhanced permeability and retention effect. Despite these favourable properties, clinical translation of nano-therapeutics is inhibited due to poor in vivo stability, biodistribution and target cell internalisation. Nano-therapeutics can be modified to exploit features of the tumour microenvironment such as elevated hypoxia, increased pH and a compromised extracellular matrix. This is in contrast to cytotoxic chemotherapies which generally do not exploit the characteristic pathological features of the tumour microenvironment, and as such are prone to debilitating systemic toxicities. This review examines strategies for tumour microenvironment targeting to improve nanoparticle delivery, with particular focus on the delivery of nucleic acids and gold nanoparticles. Evidence for key research areas and future technologies are presented and critically evaluated. Among the most promising technologies are the development of next-generation cell penetrating peptides and the incorporation of micro-environment responsive stealth molecules.

In our earlier work, we identified microRNA-10b (miR10b) as a master regulator of the viability of metastatic tumor cells. This knowledge allowed us to design a miR10b-targeted therapeutic consisting of anti-miR10b and ultrasmall iron oxide magnetic nanoparticles (MN), termed MN-anti-miR10b. In mouse models of breast cancer, we demonstrated that MN-anti-miR10b caused durable regressions of established metastases with no evidence of systemic toxicity. As a first step towards translating MN-anti-miR10b for the treatment of metastatic breast cancer, we needed to determine if MN-anti-miR10b, which is so effective in mice, will also accumulate in human metastases.

C fullerene-based nanoformulations are proposed to have a direct toxic effect on tumor cells. Previous investigations demonstrated that C fullerene used alone or being conjugated with chemotherapeutic agents possesses a potent anticancer activity. The main aim of this study was to investigate the effect of C fullerene and its nanocomplexes with anticancer drugs on human phagocyte metabolic profile in vitro.

In this study, we report on the synthesis, imaging, and radiosensitizing properties of ultrasmall β-NaGdF:Yb50% nanoparticles as a multifunctional theranostic platform. The synthesized nanoparticles act as potent bimodal contrast agents with superior imaging properties compared to existing agents used for magnetic resonance imaging (MRI) and computed tomography (CT). Clonogenic assays demonstrated that these nanoparticles can act as effective radiosensitizers, provided that the nanoparticles are taken up intracellularly.