Radiation therapy induces immunogenic cell death, which can theoretically stimulate T cell priming and induction of tumor-specific memory T cell responses, serving as an in situ vaccine. In practice, this abscopal effect is rarely observed. We use two mouse models of pancreatic cancer to show that a single dose of stereotactic body radiation therapy (SBRT) synergizes with intratumoral injection of agonistic anti-CD40, resulting in regression of non-treated contralateral tumors and formation of long-term immunologic memory. Long-term survival was not observed when mice received multiple fractions of SBRT, or when TGFβ blockade was combined with SBRT. SBRT and anti-CD40 was so effective at augmenting T cell priming, that memory CD8 T cell responses to both tumor and self-antigens were induced, resulting in vitiligo in long-term survivors.

Nanotechnology has opened up a new, previously unimaginable world in cancer diagnosis and therapy, leading to the emergence of Cancer Nanomedicine and nanoparticle-aided radiotherapy. Smart nanomaterials (nanoparticle drones) can now be constructed with capability to precisely target cancer cells and be remotely activated with radiation to emit micrometer-range missile-like electrons to destroy the tumor cells. These nanoparticle drones can also be programmed to deliver therapeutic payloads to tumor sites to achieve optimal therapeutic efficacy. In this article we examine the state-of-the-art and potential of nanoparticle drones in targeting lung cancer. Inhalation (air) versus traditional intravenous (‘sea’) routes of navigating physiological barriers using such drones is assessed. Results and analysis suggest that inhalation route may offer more promise for targeting tumor cells with radiosensitizers and cannabinoids from the perspective of maximizing damage to lung tumors cells while minimizing any collateral damage or side effects.

In efforts to overcome current challenges in cancer treatment, multifunctional nanoparticles are attracting growing interest, including nanoparticles made with polydopamine (PDA). PDA is a nature-inspired polymer with a dark brown color. It has excellent biocompatibility and is biodegradable, offering a range of extraordinary inherent advantages. These include excellent drug loading capability, photothermal conversion efficiency, and adhesive properties. Though the mechanism of dopamine polymerization remains unclear, PDA has demonstrated exceptional flexibility in engineering desired morphology and size, easy and straightforward functionalization, etc. Moreover, it offers enormous potential for designing multifunctional nanomaterials for innovative approaches in cancer treatment. The aim of this work is to review studies on PDA, where the potential to develop multifunctional nanomaterials with applications in photothermal therapy has been demonstrated. Future prospects of PDA for developing applications in enhancing radiotherapy and/or immunotherapy, including for image-guided drug delivery to boost therapeutic efficacy and minimal side effects, are presented.

Pancreatic cancer is particularly refractory to modern therapies, with a 5-year survival rate for patients at a dismal 8%. One of the significant barriers to effective treatment is the immunosuppressive pancreatic tumor microenvironment and development of resistance to treatment. New treatment options to increase both the survival and quality of life of patients are urgently needed. This study reports on a new non-cannabinoid, non-psychoactive derivative of cannabis, termed FBL-03G, with the potential to treat pancreatic cancer. In vitro results show major increase in apoptosis and consequential decrease in survival for two pancreatic cancer models- Panc-02 and KPC pancreatic cancer cells treated with varying concentrations of FBL-03G and radiotherapy. Meanwhile, in vivo results demonstrate therapeutic efficacy in delaying both local and metastatic tumor progression in animal models with pancreatic cancer when using FBL-03G sustainably delivered from smart radiotherapy biomaterials. Repeated experiments also showed significant (P < 0.0001) increase in survival for animals with pancreatic cancer compared to control cohorts. The findings demonstrate the potential for this new cannabis derivative in the treatment of both localized and advanced pancreatic cancer, providing impetus for further studies toward clinical translation.

Over the years, many in vitro and in vivo studies have shown the antineoplastic effects of cannabinoids (CBDs), with reports advocating for investigations of combination therapy approaches that could better leverage these effects in clinical translation. This study explores the potential of combination approaches employing CBDs with radiotherapy (RT) or smart biomaterials toward enhancing therapeutic efficacy during treatment of pancreatic and lung cancers. In in vitro studies, clonogenic assay results showed greater effective tumor cell killing, when combining CBDs and RT. Meanwhile, in vivo study results revealed major increase in survival when employing smart biomaterials for sustained delivery of CBDs to tumor cells. The significance of these findings, considerations for further research, and viable roadmap to clinical translation are discussed.

Nanoparticle-aided radiation therapy is emerging as a promising modality to enhance radiotherapy via the radiosensitizing action of high atomic number (Z) nanoparticles. However, the delivery of sufficiently potent concentrations of such nanoparticles to the tumor remain a challenge. This study investigates the dose enhancement to lung tumors due to high-Z nanoparticles (NPs) administered via inhalation during external beam radiotherapy. Here NPs investigated include: cisplatin nanoparticles (CNPs), carboplatin nanoparticles (CBNPs), and gold nanoparticles (GNPs). Using Monte Carlo–generated megavoltage energy spectra, a previously employed analytic method was used to estimate dose enhancement to lung tumors due to radiation-induced photoelectrons from the NPs administered via inhalation route (IR) in comparison to intravenous (IV) administration. Previous studies have indicated about 5% of FDA-approved cisplatin concentrations reach the lung via IV. Meanwhile recent experimental studies indicate that 3.5–14.6 times higher concentrations of NPs can reach the lung by IR compared to IV. Taking these into account, the dose enhancement factor (DEF) defined as the ratio of the radiotherapy dose with and without nanoparticles was calculated for a range of NPs concentrations and tumor sizes. The DEF for IR was then compared with that for IV. For IR with 3.5 times higher concentrations than IV, and 2 cm diameter tumor, clinically significant DEF values of up to 1.19, 1.26, and 1.51 were obtained for CNPs, CBNPs and GNPs. In comparison values of 1.06, 1.08, and 1.15 were obtained via IV administration. For IR with 14.6 times higher concentrations, even higher DEF values were obtained e.g. 1.81 for CNPs. Results also showed that the DEF increased with increasing field size or decreasing tumor volume, as expected. The results of this work indicate that IR administration of targeted high-Z CNPs/CBNPs/GNPs could enable clinically significant DEF to lung tumors compared to IV administration during external beam radiotherapy. For FDA approved concentrations of CNPs or CBNPs considered, this could allow for additional dose enhancement to tumors via photoelectric mechanism during concomitant chemoradiotherapy.