Combined Chemo Research Articles

Abstract 3411: Biological subtypes of nasopharyngeal carcinoma by genomic profiling

Abstract Objective: Nasopharyngeal carcinoma (NPC) is a common Epstein-barr virus-associated epithelial malignancy in several parts of the world including Southeast Asia. While the majority of patients are treated uniformly with a combination of chemo and radiation therapy, 20% of patients experience recurrence, most commonly in the form of distant metastasis. NPC subtypes based on underlying differences in biology are unexplored and are likely responsible for the heterogeneous clinical response. As NPC biopsies are small and have significant stromal infiltrate, obtaining pure epithelial cells for genomic profiling is a challenge. We aim to overcome these limitations to identify biological subtypes and dysregulated molecular pathways in NPC. Methods: We first evaluated 217 whole exomes sequences, including 102 microdissected tumors, from three previous studies for single nucleotide variants and copy number changes, following GATK standards and using next generation sequencing copy number callers. We then applied a novel method for gene expression profiling developed in our lab to a new cohort of EBV-positive primary NPC cases from our institution. We performed laser capture microdissection, separately dissecting tumor, normal and microenvironment for each case. We applied Smart-3SEQ, a novel 3' end RNA-Seq technique which allows for the accurate quantification of transcript abundance in dissected FFPE samples comprising only a few hundred cells. Results: We achieved a per-base concordance of 80.4% between copy number profiles by SNP array and whole exome sequencing. Unsupervised clustering identified three distinct copy-number groups of NPC tumors, with a low copy-number group demonstrating an 18.7% better 5-year disease-specific survival, not attributable to stage. Apart from broad cytogenetic changes, narrow regions of amplifications (e.g. 1q21, 11q13) and deletions (e.g. 9p21, 11q22) were important for defining copy-number subtypes. Preliminary differential gene expression analysis showed that genes involved in cell cycle and cellular differentiation were significantly dysregulated in tumor cells (p < 0.001 and p = 0.03 respectively), while genes involved in cilia assembly and flagella transport were upregulated in normal cells (p < 0.001 for both). Our further analysis includes defining tumor subtypes based on gene expression, identifying key driver pathways, and correlating with EBV-latent gene expression, the immune environment, as well as clinical outcome. Conclusion: NPC tumors are biologically heterogeneous and can be classified based on their mutational and gene expression profiles. This provides an important basis for the consideration of escalation and de-escalation of therapy in selected patient groups. Citation Format: Kai Xun Joshua Tay, Chunfang Zhu, Sujay Vennam, Sushama Varma, Quynh-Thu Le, John Sunwoo, Robert West. Biological subtypes of nasopharyngeal carcinoma by genomic profiling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3411.

Clinical experience with combination chemo-/immunotherapy using trabectedin and nivolumab for advanced soft tissue sarcoma.

e23568Background: Immune checkpoint inhibitors revive pre-existing immune responses that are suppressed in cancer. To restore tumor surveillance that is lost in cancer patients, a tumoricidal agent...

Effect of different chemotherapy regimens on pathological response in the preoperative combined chemo radiotherapy of rectal adenocarcinomas: A retrospective analysis.

e15564Background: To investigate the influence of different neoadjuvant chemotherapy modalities on Tumor Regression Grading Methods: We analyzed a total of 80 patients (pts) with locally advanced s...

Porous hollow palladium nanoplatform for imaging-guided trimodal chemo-, photothermal-, and radiotherapy

Cancer is one of the major causes of human death. There are many types of cancer treatment including surgery, chemotherapy, radiotherapy, and photothermal therapy. Combining different therapies can synergistically enhance the therapeutic effect. We developed porous hollow palladium nanoparticles (PHPdNPs) to co-deliver 131I (a radioisotope that is commonly used in radiotherapy) and doxorubicin (DOX; a chemotherapy drug). Compared with other mesoporous nanocarriers, our PHPdNPs exhibited impressive photothermal conversion efficiency and stability. Drug loading is high and drug release is controllable by repeated laser irradiation and acidic pH in tumor microenvironments. Owing to the specific interaction between palladium and iodine, the PHPdNPs serve as effective 131I delivery vehicles with excellent radiochemical stability. A single dose of [131I]PHPdNPs-DOX has superior antitumor efficacy because it enables a combination of chemo-, photothermal-, and radio-therapy. Moreover, the nanocomplex has no obvious side-effects in mice. Therefore, we believe that PHPdNPs are excellent candidates for multimodal imaging-guided therapy.

Role of 18F-FDG PET/CT in post-operative assessment and therapeutic follow up of renal cell carcinoma

ObjectiveThe aim of this study was to evaluate the role of PET/CT in post-operative assessment and therapeutic follow up of renal cell carcinoma (RCC). Patients and methods30 patients having pathologically proven RCC underwent PET/CT examination following a preset protocol as baseline study within 1 month post radical nephrectomy. They all had a second PET/CT examination following the same protocol after 6 to 12 months as systematic follow up or to assess the therapeutic response. Results13 out of 30 patients (43.3%) were performing their regular follow up post radical nephrectomy, 14 cases (46.7%) were under chemotherapy while 3 cases (10%) were receiving combined chemo and radiotherapy.In first setting follow up examination 18F-FDG PET/CT showed 17 true positive (TP), 12 true negative (TN) and 1 false negative (FN) cases while CT showed 11 TP, 11 TN, 7 FN and 1 false positive (FP) cases. 18F-FDG PET/CT vs. CT revealed sensitivity, specificity and accuracy of 94.4% vs. 61.1%, 100% vs. 91.7% and 96.7% vs.73.3% respectively. Conclusion18F-FDG PET/CT is more accurate than CT in post-operative and therapeutic follow up of renal cell carcinoma.

The combined therapeutic effects of 131iodine-labeled multifunctional copper sulfide-loaded microspheres in treating breast cancer

Compared to conventional cancer treatment, combination therapy based on well-designed nanoscale platforms may offer an opportunity to eliminate tumors and reduce recurrence and metastasis. In this study, we prepared multifunctional microspheres loading 131I-labeled hollow copper sulfide nanoparticles and paclitaxel (131I-HCuSNPs-MS-PTX) for imaging and therapeutics of W256/B breast tumors in rats. 18F-fluordeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) imaging detected that the expansion of the tumor volume was delayed (P<0.05) following intra-tumoral (i.t.) injection with 131I-HCuSNPs-MS-PTX plus near-infrared (NIR) irradiation. The immunohistochemical analysis further confirmed the anti-tumor effect. The single photon emission computed tomography (SPECT)/photoacoustic imaging mediated by 131I-HCuSNPs-MS-PTX demonstrated that microspheres were mainly distributed in the tumors with a relatively low distribution in other organs. Our results revealed that 131I-HCuSNPs-MS-PTX offered combined photothermal, chemo- and radio-therapies, eliminating tumors at a relatively low dose, as well as allowing SPECT/CT and photoacoustic imaging monitoring of distribution of the injected agents non-invasively. The copper sulfide-loaded microspheres, 131I-HCuSNPs-MS-PTX, can serve as a versatile theranostic agent in an orthotopic breast cancer model.

The hybrid PLGA‐based nanoparticles as a smart nanoplatform for imaging‐guided and near‐Infrared light‐triggered combination cancer therapy

Cancer theranostics, the combination of imaging and therapeutic agents in a smart nanocarriers, has been a promising approach towards cancer [1]. And the chemotherapy combining with photothermal therapy to treat tumors can efficiently improve therapeutic efficacies [2].Herein, we report a theranostic nanoplatform based on PLGA nanoparticles, which are constructed by simultaneous encapsulating indocyanine green (ICG), a widely used near‐infrared (NIR) dye in photothermal therapy, and doxorubicin (Dox), a chemotherapy drug, into biodegradable poly(D, L‐lactic‐co‐glycolic acid) (PLGA) polymeric nanoparticles and decorated with bovine serum albumin (BSA) using the double emulsion solvent evaporation method (W/O/W). The as fabricated IDP NPs with the mean diameter of 220 nm exhibited good dispersity, excellent size stability, especially enhanced photostability (fluorescence stability) compared with free ICG, and is able to efficiently load chemotherapeutic drug doxorubicin (Dox) into the PLGA core. When the weight ratio of added ICG to Dox was 0.075 (μg ICG/μg Dox), the encapsulation efficiency of the Dox and ICG can be reached approximately 42.0% and 55.3%, respectively. It was confirmed that IDP NPs showed preferable photothermal effect, favorable photoacoustic (PA) imaging properties and faster release of Dox when exposed to near‐infrared (NIR) laser irradiation or acidic conditions. Moreover, the NIR light‐induced photothermal heat can enhance the permeability of the lysosomal membrane resulting in efficient Dox translocation from lysosomes to cytoplasm indicating by intracellular distribution assay. In comparison with the chemo‐ or photothermal treatment alone, the combined treatment of IDP NPs with laser irradiation achieving a marked synergistic therapeutic effect. The tumor cell viability was ~5% when treated with IDP NPs ([ICG] =15 μg/mL, [Dox] =3.9 μg/mL) under NIR laser irradiation (808 nm, 1.5 W/cm2). Our work validates that the developed co‐loaded BSA‐decorated IDP NPs could serve as a promising platform for PA imaging‐guided combined chemo‐ and photothermal therapy with reducing side effects in cancer theranostics.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Cyclodextrin-Based Magnetic Nanoparticles for Cancer Therapy.

Polydopamine (PDA)-coated magnetic nanoparticles functionalized with mono-6-thio-β-cyclodextrin (SH-βCD) were obtained and characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), Nuclear and Magnetic Resonance Imaging (NMR and MRI), and doxorubicin (DOXO)-loading experiments. The liver cancer cellular internalization of DOXO-loaded nanoparticles was investigated by confocal imaging microscopy. Synthesized nanomaterials bearing a chemotherapeutic drug and a layer of polydopamine capable of absorbing near-infrared light show high performance in the combined chemo- and photothermal therapy (CT-PTT) of liver cancer due to the synergistic effect of both modalities as demonstrated in vitro. Moreover, our material exhibits improved T2 contrast properties, which have been verified using Carr-Purcell-Meiboom-Gill pulse sequence and MRI Spin-Echo imaging of the nanoparticles dispersed in the agarose gel phantoms. Therefore, the presented results cast new light on the preparation of polydopamine-based magnetic theranostic nanomaterials, as well as on the proper methodology for investigation of magnetic nanoparticles in high field MRI experiments. The prepared material is a robust theranostic nanoasystem with great potential in nanomedicine.

Dual-Targeted Selenium Nanoparticles for Synergistic Photothermal Therapy and Chemotherapy of Tumors.

A combination of chemo- and photothermal therapy has emerged as a promising tactic for cancer therapy. However, the intricacy of accurate delivery and the ability to initiate drug release in specific tumor sites remains a challenging puzzle. Hence, to assure that the chemotherapeutic drug and photothermal agent are synchronously delivered to a tumor area for their synergistic effect, dual-target (RC-12 and PG-6 peptides) functionalized selenium nanoparticles loaded with both doxorubicin (DOX) and indocyanine green (ICG) were designed and successfully synthesized. The as-synthesized nanoparticles exhibited good monodispersity, size stability, and consistent spectral characteristics compared with those of ICG or DOX alone. The nanoparticles underwent self-immolated cleavage under irradiation from a near-IR laser and released the loaded drug owing to sufficient hyperthermia. Moreover, the internalized nanoparticles triggered the overproduction of intracellular reactive oxygen species to induce cell apoptosis. Taken together, this study provides a sequentially triggered nanosystem to achieve precise drug delivery by chemo-photothermal combination.

Light-Activatable Red Blood Cell Membrane-Camouflaged Dimeric Prodrug Nanoparticles for Synergistic Photodynamic/Chemotherapy.

Biomimetic approach offers numerous opportunities to design therapeutic platforms with enhanced antitumor performance and biocompatibility. Herein we report red blood cell membrane-camouflaged nanoparticles (RBC(M(TPC-PTX))) for synergistic chemo- and photodynamic therapy (PDT). Specifically, the inner core is mainly constructed by reactive oxygen species (ROS)-responsive PTX dimer (PTX2-TK) and photosensitizer 5,10,15,20-tetraphenylchlorin (TPC). In vitro experiments show that the prepared RBC(M(TPC-PTX)) is readily taken up into endosomes. Under appropriate light irradiation, the TPC can generate ROS, not only for PDT but also for triggering PTX2-TK cleavage and on-demand PTX release for chemotherapy. In vivo results show that the coating of RBC membrane prolongs blood circulation and improves tumor accumulation. The combination of chemo- and photodynamic therapy enhances anticancer therapeutic activity, and light-triggered drug release reduces systematic toxicity. All these characteristics render the described technology extremely promising for cancer treatment.

Opportunities and challenges for combining chemo- and biocatalysis

The past decade has seen a substantial increase in successful examples of the combination of chemo- and biocatalysis for multistep syntheses. This is driven by obvious advantages such as higher yields, decreased costs, environmental benefits and high selectivity. On the downside, efforts must be undertaken to combine the divergent reaction conditions, reagent tolerance and solvent systems of these ‘different worlds of catalysis’. Owing to progress in enzyme discovery and engineering, as well as in the development of milder and more compatible conditions for operating with various chemocatalysts, many historical limitations can already be overcome. This Review highlights the opportunities available in the chemical space of combined syntheses using prominent examples, but also discusses the current challenges and emerging solutions, keeping in mind the fast progress in transition metal-, organo-, photo-, electro-, hetero- and biocatalysis. Chemical and biological catalysts provide distinct advantages and disadvantages to the synthetic chemist. This Review focuses on efforts to combine chemo- and biocatalysts, outlining the opportunities achievable by this approach and also efforts to overcome any incompatibilities between these different systems.

Multifunctional nanoparticles as somatostatin receptor-targeting delivery system of polyaniline and methotrexate for combined chemo–photothermal therapy

Lanreotide (LT), a synthetic analog of somatostatin, has been demonstrated to specifically bind to somatostatin receptors (SSTRs), which are widely overexpressed in several types of cancer cells. In this study, we incorporated a chemotherapeutic agent, methotrexate (MTX), and a photosensitizer material, polyaniline (PANI), into hybrid polymer nanoparticles (NPs), which could target cancer cells after conjugation with LT (LT-MTX/PANI NPs). The successful preparation of LT–MTX/PANI NPs was confirmed by a small particle size (187.9 ± 3.2 nm), a polydispersity index of 0.232 ± 0.011, and a negative ζ potential of −14.6 ± 1.0 mV. Notably, LT-MTX/PANI NPs showed a greater uptake into SSTR-positive cancer cells and thereby better inhibited cell viability and induced higher levels of apoptosis than MTX, PANI NP, and MTX/PANI NP treatments did. In addition, the heat associated with the burst drug release induced by near-infrared (NIR) irradiation resulted in remarkably enhanced cell apoptosis, which was confirmed by an increase in the expression levels of apoptotic marker proteins. In agreement with the in vitro results, the administration of the SSTR-targeting NPs, followed by NIR exposure, to xenograft tumor-bearing mice resulted in an improved suppression of tumor development compared to that shown by MTX, PANI NPs, and MTX/PANI NPs, as well as by LT-MTX/PANI NPs without photothermal therapy. Thus, the SSTR-targeting NPs could be a promising delivery system for the effective treatment of SSTR-positive cancers. Statement of significanceSomatostatin receptors are widely overexpressed in several types of cancer cells. In this study, we designed nanoparticles for targeted delivery of chemotherapeutic agents to tumor sites by conjugating hybrid polymers with a synthetic analog of somatostatin, specifically binding to somatostatin receptors. In addition, a photosensitizer material, polyaniline, was incorporated into the nanoparticles for combined chemo–photothermal therapy. The results demonstrated clear advantages of the newly designed targeted nanoparticles over their non-targeted counterparts or a free chemotherapeutic drug in inhibiting the viability of cancer cells in vitro and targeting/suppressing the tumor growth in an animal xenograft model. The study suggests that the designed nanoparticles are a promising delivery system for the effective treatment of somatostatin receptor-positive cancers.

Combination Chemo in Advanced Pancreatic Adenocarcinoma

Combination Chemo in Advanced Pancreatic Adenocarcinoma

Clinical features and surgical outcomes of pulmonary artery sarcoma

ObjectivePulmonary artery sarcoma is an exceedingly rare malignancy. There is a lack of consensus regarding its diagnosis and treatment. We reviewed our experience in the surgical management of pulmonary artery sarcoma over an 11-year period. MethodsFrom January 2005 to February 2016, 12 patients with pulmonary artery sarcoma (age 51 ± 14 years, 5 male) underwent surgical treatment at our center. Nine patients (75%) exhibited pulmonary trunk involvement on computed tomography angiography. Six patients (50%) were initially misdiagnosed with pulmonary embolism. ResultsTen patients underwent pulmonary endarterectomy, and 3 of these patients required additional unilateral pneumonectomy. The remaining 2 patients underwent exploratory thoracotomy. One patient (8.3%) died in the hospital. The median length of postoperative intensive care unit and hospital stay were 1 day (range, 1-15 days) and 8 days (range, 5-21 days), respectively. The median postoperative survival of the total series was 18 months. Patients who received postoperative combined chemo- and radiotherapy were associated with improved survival compared with those who had isolated adjuvant therapy or surgery alone (median survival 28 vs 8 months, P = .042). ConclusionsAlthough pulmonary artery sarcoma has a very poor prognosis, surgical treatment offers a chance for symptom relief and better long-term outcome. Aggressive postoperative adjuvant treatment may be necessary to improve survival.

Sequential Delivery of Doxorubicin and Zoledronic Acid to Breast Cancer Cells by CB[7]-Modified Iron Oxide Nanoparticles.

Drug-loaded magnetic nanoparticles were synthesized and used for the sequential delivery of the antiresorptive agent zoledronic acid (Zol) and the cytotoxic drug doxorubicin (Dox) to breast cancer cells (MCF-7). Zol was attached to bare iron oxide nanoparticles (IONPs) via phosphonate coordination to form Z-NPs. The unbound imidazole of Zol was then used to complex the organic macrocycle CB[7] to obtain CZ-NPs. Dox was complexed to the CZ-NPs to form the fully loaded particles (DCZ-NPs), which were stable in solution at 37 °C and physiological pH (7.4). Fluorescence spectroscopy established that Dox is released in solution from DCZ-NPs suddenly (i) when the particles are subjected to magnetically induced heating to 42 °C at low pH (5.0) and (ii) in the presence of glutathione (GSH). Mass spectrometry indicated that Zol is released slowly in solution at low pH after Dox release. Magnetic measurements with a magnetic reader revealed that DCZ-NPs are internalized preferentially by MCF-7 cells versus nonmalignant cells (HEK293). Zol and Dox acted synergistically when delivered by the particles. DCZ-NPs caused a decrease in the viability of MCF-7 cells that was greater than the net decrease caused when the drugs were added to the cells individually at concentrations equivalent to those delivered by the particles. MCF-7 cells were treated with DCZ-NPs and subjected to an alternating magnetic field (AMF) which, with the nanoparticles present, raised the temperature of the cells and triggered the intracellular release of Dox, as indicated by fluorescence activated cell sorting (FACS). The cytotoxic effects of the DCZ-NPs on MCF-7 cells were enhanced 10-fold by AMF-induced heating. DCZ-NPs were also able to completely inhibit MCF-7 cell adhesion and invasion in vitro, indicating the potential of the particles to act as antimetastatic agents. Together these results demonstrate that DCZ-NPs warrant development as a system for combined chemo- and thermo-therapeutic treatment of cancer.

HSP90 Inhibition Enhances the Anti-Tumor Efficacy of Combination Chemo Immunotherapy Targeting DNA Repair Proteins

HSP90 Inhibition Enhances the Anti-Tumor Efficacy of Combination Chemo Immunotherapy Targeting DNA Repair Proteins

Multifunctional gold nanorods and docetaxel-encapsulated liposomes for combined thermo- and chemotherapy.

Personalized and precise nanomedicines are highly demanded for today’s medical needs. Liposomes are ideal candidates for the construction of multifunctional drug delivery systems. In this study, a liposome was used to improve the clinical issues of docetaxel (Doc), a potent antimitotic chemotherapy for prostate cancer (PC). RLT, a low-density lipoprotein receptor (LDLR)-binding peptide, and PEG were conjugated to the liposomes, and gold nanorods (GNRs) were also incorporated into the liposomes. The GNRs/Doc-liposome-RLT (GNRs/DocL-R) was tested in PC-3 cells and in PC-3 tumor-bearing nude mice. Results showed that GNRs/DocL-R possessed a diameter approximately 163.15±1.83 nm and a zeta potential approximately −32.8±2.16 mV. GNRs/DocL-R showed enhanced intracellular entrance, increased accumulation in the implanted tumor region, and the highest tumor inhibition in vitro and in vivo. Therefore, the multifunctional GNRs/DocL-R was a potential cancer treatment via combined chemo- and thermotherapy.

Amphiphilic Near-Infrared Conjugated Polymer for Photothermal and Chemo Combination Therapy.

Amphiphilic conjugated polymer was designed and utilized as nanocarriers without further general encapsulation using PEGylated materials for photothermal therapy (PTT) and chemotherapy. These nanocarriers have maximum absorption in ideal phototherapeutic window between 800 and 850 nm and excellent photothermal conversion efficiency of 76% at 808 nm. It provides the simultaneous therapy of chemotherapy and PTT with the monitoring of photoacoustic imaging. After combined therapy via tail vein injection, complete remission and no recurrence of tumors can be observed over a course of 20 days, indicating these amphiphilic NPs has great potential for NIR photoacoustic imaging-guided photothermal and chemo combined therapy.

Porous NH2-MIL-125 as an efficient nano-platform for drug delivery, imaging, and ROS therapy utilized Low-Intensity Visible light exposure system

Metal-organic frameworks are a novel class of organic-inorganic hybrid polymer with potential applications in bioimaging, drug delivery, and ROS therapy. NH2-MIL-125, which is a titanium-based metal organic framework with a large surface area of 1540m2/g, was synthesized using a hydrothermal method. The material was characterized by powder X-ray diffreaction (PXRD), thermogravimetric analysis (TGA), and transmission electron microscopy (TEM), and N2 isotherm analyses. The size of the polymer was reduced to the nanoscale using a high-frequency sonication process. PEGylation was carried out to improve the stability and bioavailability of the NMOF. The as-synthesized nano-NH2-MIL-125/PEG (NMOF/PEG) exhibited good biocompatibility over the (Cancer) MCF-7 and (Normal) COS-7 cell line. The interaction of NMOF/PEG with the breast cancer cell line (MCF-7) was examined by BIO-TEM analysis and laser confocal imaging. 2′,7′–dichlorofluorescin diacetate (DCFDA) analysis confirmed that NMOF/PEG produced free radicals inside the cancer cell line (MCF-7) upon visible light irradiation. NMOF/PEG absorbed a large amount of DOX (20wt.% of DOX) and showed pH, and photosensitive release. This controlled drug delivery was attributed to the presence of NH2, Ti group in MOF and a hydroxyl group in PEG. This combination of chemo- and ROS-therapy showed excellent efficiency in killing cancer MCF-7 cells.

Nutlin‐3a and Cytokine Co‐loaded Spermine‐Modified Acetalated Dextran Nanoparticles for Cancer Chemo‐Immunotherapy

AbstractThe combination of chemo‐ and immunotherapy represents one promising strategy to overcome the existent challenges in the present‐day anticancer therapy. Here, spermine‐modified acetalated dextran nanoparticles (Sp‐AcDEX NPs), co‐loaded with the non‐genotoxic molecule Nutlin‐3a (Nut3a), and the cytokine granulocyte–macrophage colony‐stimulating factor (GM‐CSF), are developed to induce cancer cell death and create a specific antitumor immune response. These polymeric NPs release Nut3a in a pH dependent fashion and induce endosomal escape. Due to Nut3a, the loaded NPs exert specific toxicity toward wild‐type p53 cancer cells while avoiding toxicity in immune cells. Furthermore, the NPs show intrinsic immune adjuvancy on monocyte derived‐dendritic cells, upregulating the expression of cell surface CD83 and CD86 costimulatory markers. Finally, it is examined that by inducing MCF‐7 breast cancer cell death and acting as immune adjuvants, the NPs can downregulate the expression of IL‐10 and upregulate IL‐1β, leading to proliferation of CD3+ and cytotoxic CD8+ T cells. Overall, the study suggests that Sp‐AcDEX NPs loaded with Nut3a and GM‐CSF is a promising system for chemo‐immunotherapy, capable of inducing tumor cell death and stimulating immune response.