Endowing Pt(IV) with Perfluorocarbon Chains and Human Serum Albumin Encapsulation for Highly Effective Antitumor Chemoimmunotherapy.

Tumor metastases and reoccurrence are considered the leading causes of cancer-associated deaths. As an emerging therapeutic method, increasing research efforts have been devoted to immunogenic cell death (ICD)-inducing compounds to solve the challenge. The clinically approved chemotherapeutic Pt complexes are not or are only poorly able to trigger ICD. Herein, the axial functionalization of the Pt(II) complex cisplatin with perfluorocarbon chains into ICD-inducing Pt(IV) prodrugs is reported. Strikingly, while the Pt(II) complex as well as the perfluorocarbon ligands did not induce ICD, the Pt(IV) prodrug demonstrated unexpectantly the induction of ICD through accumulation in the endoplasmic reticulum and generation of reactive oxygen species in this organelle. To enhance the pharmacological properties, the compound was encapsulated with human serum albumin into nanoparticles. While selectively accumulating in the tumorous tissue, the nanoparticles demonstrated a strong tumor growth inhibitory effect against osteosarcoma inside a mouse model. In vivo tumor vaccine analysis also demonstrated the ability of Pt(IV) to be an ideal ICD inducer. Overall, this study reports on axially perfluorocarbon chain-modified Pt(IV) complexes for ICD induction and chemoimmunotherapy in osteosarcoma.

Antibody-platinum (IV) prodrugs conjugates for targeted treatment of cutaneous squamous cell carcinoma.

Antibody-drug conjugates (ADCs) are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells, thereby attracting considerable attention in precise oncology therapy. Cetuximab (Cet) is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma (cSCC); however, its anti-tumor activity is limited to a single use. Cisplatin (CisPt) shows good curative effects; however, its adverse effects and non-tumor-targeting ability are major drawbacks. In this study, we designed and developed a new ADC based on a new cytotoxic platinum (IV) prodrug (C8Pt(IV)) and Cet. The so-called antibody-platinum (IV) prodrugs conjugates, named Cet-C8Pt(IV), showed excellent tumor targeting in cSCC. Specifically, it accurately delivered C8Pt(IV) into tumor cells to exert the combined anti-tumor effect of Cet and CisPt. Herein, metabolomic analysis showed that Cet-C8Pt(IV) promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells, thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum (IV) prodrugs conjugates.

Revolutionizing sphincter preservation in ultra-low rectal cancer: exploring the potential of transanal endoscopic intersphincteric resection (taE-ISR): a propensity score-matched cohort study.

BACKGROUND: With the optimization of neoadjuvant treatment regimens, the indications for intersphincteric resection (ISR) have expanded. However, limitations such as unclear surgical field, impaired anal function, and failure of anal preservation still exist. Transanal total mesorectal excision can complement the drawbacks of ISR. Therefore, this study combined these two techniques and proposed transanal endoscopic intersphincteric resection (taE-ISR), aiming to explore the value of this novel technique in anal preservation for ultra-low rectal cancer. MATERIAL AND METHODS: Four high-volume centres were involved. After 1:1 propensity score-matching, patients with ultra-low rectal cancer underwent taE-ISR ( n =90) or ISR ( n =90) were included. Baseline characteristics, perioperative outcomes, pathological results, and follow-up were compared between the two groups. A nomogram model was established to assess the potential risks of anal preservation. RESULTS: The incidence of adjacent organ injury (0.0% vs. 5.6%, P =0.059), positive distal resection margin (1.1% vs. 8.9%, P =0.034), and incomplete specimen (2.2% vs. 13.3%, P =0.012) were lower in taE-ISR group. Moreover, the anal preservation rate was significantly higher in taE-ISR group (97.8% vs. 82.2%, P =0.001). Patients in the taE-ISR group showed a better disease-free survival ( P =0.044) and lower cumulative recurrence ( P =0.022) compared to the ISR group. Surgery procedure, tumour distance, and adjacent organ injury were factors influencing anal preservation in patients with ultra-low rectal cancer. CONCLUSION: taE-ISR technique was safe, feasible, and improved surgical quality, anal preservation rate and survival outcomes in ultra-low rectal cancer patients. It held significant clinical value and showed promising application prospects for anal preservation.

Natural orifice specimen extraction surgery versus small-incision assisted laparoscopic radical right hemicolectomy.

Conventional laparoscopic-assisted right hemicolectomy requires a small abdominal incision to extract the specimen, which becomes an important source of postoperative complications and impairs perioperative experience. Transvaginal natural orifice specimen extraction surgery (NOSES VIIIA) avoids this small incision by extracting the specimen through the vagina. Here we describe the design of a multicenter, open-label, parallel, noninferior, phase III randomized controlled trial (NCT05495048). The aim of this study is to confirm that the NOSES VIIIA procedure is not inferior to small-incision assisted right hemicolectomy in long-term oncological efficacy. A total of 352 female patients with right colon adenocarcinoma/high-grade intraepithelial neoplasia will be randomly assigned to the NOSES VIIIA arm and the small-incision arm in a 1:1 ratio. The primary end point of this trial is 3 year disease-free survival. Clinical Trial Registration: NCT05495048 (ClinicalTrials.gov).

Disulfide-containing polymer delivery of C527 and a Platinum(IV) prodrug selectively inhibited protein ubiquitination and tumor growth on cisplatin resistant and patient-derived liver cancer models.

USP1 (Ubiquitin-specific protease 1) is closely related to the prognosis of patients with liver cancer and plays an important role in DNA damage repair. C527 is a selective USP1 inhibitor (USP1i), which can regulate the protein ubiquitination to effectively inhibit the proliferation of cancer cells. However, its clinical application is hindered due to the poor water solubility and lack of tumor targeting. Moreover, the efficacy of single use of USP1i is still limited. Herein, a glutathione (GSH) sensitive amphiphilic polymer (poly (2-HD-co-HPMDA)-mPEG, PHHM) with disulfide bonds in the main chain was designed to encapsulate the USP1i as well as platinum (IV) prodrug (Pt (IV)-C12), resulting in the formation of composite nanoparticles, i.e., NP-Pt-USP1i. NP-Pt-USP1i can inhibit the DNA damage repair by targeting USP1 by the encapsulated USP1i, which ultimately increases the sensitivity of tumor cells to cisplatin and enhances the anti-cancer efficacy of cisplatin. Finally, an intraperitoneal tumor mice model and a patient-derived xenograft (PDX) of liver cancer mice model were established to prove that NP-Pt-USP1i could effectively inhibit the tumor growth. This work further validated the possibility of therapeutically target USP1 by USP1i in combination with DNA damaging alkylating agents, which could become a promising cancer treatment modality in the future.

Safety and feasibility of laparoscopic surgery for colorectal and gastric cancer under the Chinese multi-site practice policy: admittance standards of competence are needed.

Background: The multi-site practice (MSP) policy has been practiced in China over 10 years. This study aimed to investigate the safety and feasibility of performing laparoscopic surgery for colorectal cancer (LSCRC) and gastric cancer (LSGC) under the Chinese MSP policy. Methods: We collected and analysed the data from 1,081 patients who underwent LSCRC or LSGC performed by one gastrointestinal surgeon in his original hospital (n = 573) and his MSP institutions (n = 508) between January 2017 and December 2020. Baseline demographics, intraoperative outcomes, post-operative recovery, and pathological results were compared between the original hospital and MSP institutions, as well as between MSP institutions with and without specific competence (surgical skill, operative instrument, perioperative multi-discipline team). Results: In our study, 690 patients underwent LSCRC and 391 patients underwent LSGC. The prevalence of post-operative complications was comparable for LSCRC (11.5% vs 11.1%, P = 0.89) or LSGC (15.2% vs 12.6%, P = 0.46) between the original hospital and MSP institutions. However, patients in MSP institutions without qualified surgical assistant(s) and adequate instruments experienced longer operative time and greater intraoperative blood loss. The proportion of patients with inadequate lymph-node yield was significantly higher in MSP institutions than in the original hospital for both LSCRC (11.5% vs 21.2%, P < 0.01) and LSGC (9.8% vs 20.5%, P < 0.01). Conclusion: For an experienced gastrointestinal surgeon, performing LSCRC and LSGC outside his original hospital under the MSP policy is safe and feasible, but relies on the precondition that the MSP institutions are equipped with qualified surgical skills, adequate operative instruments, and complete perioperative management.

Light triggered release of a triple action porphyrin-cisplatin conjugate evokes stronger immunogenic cell death for chemotherapy, photodynamic therapy and cancer immunotherapy.

Photodynamic therapy (PDT) has emerged as an attractive therapeutic approach which can elicit immunogenic cell death (ICD). However, current ICD inducers are still very limited as the representative ICD induces of photosensitizers can only evoke insufficient ICD to achieve unsatisfactory cancer immunotherapy. Herein, we demonstrated the use of a triple action cationic porphyrin-cisplatin conjugate (Pt-1) for drug delivery by a reactive oxygen species (ROS) sensitive polymer as nanoparticles (NP@Pt-1) for combined chemotherapy, PDT and immunotherapy. This unique triple action Pt-1 contains both chemotherapeutic Pt drugs and Porphyrin as a photosensitizer to generate ROS for PDT. Moreover, the ROS generated by Pt-1 can on the one hand degrade polymer carriers to release Pt-1 for chemotherapy and PDT. On the other hand, the ROS generated by Pt-1 subsequently triggered the ICD cascade for immunotherapy. Taken together, we demonstrated that NP@Pt-1 were the most effective and worked in a triple way. This study could provide us with new insight into the development of nanomedicine for chemotherapy, PDT as well as cancer immunotherapy.

Rotor strength and critical speed analysis of a vertical long shaft fire pump connected with different shaft lengths.

The vertical long shaft fire pump (VLSFP) is mainly used in fire-fighting places far away from land and lacking large amounts of water supply. The paper selected the XBC18-178-240LC3 model of VLSFP as the research object. First, the experimental-numerical hydraulic performance of the single-VLSFP was carried out, and then the hydraulic performance of the multi-VLSFP was analyzed by the same numerical simulation method as single-VLSFP. After that, three rotor models (Z4 model, Z5 model-original model and Z6 model) were designed by modeling software, connected by different length and number of the shaft section under the same total length of the intermediate shafts. Finally, the rotor's strength and critical speed of three models were analyzed and checked via the CFD simulation and the Workbench software. The study mainly found: (1) Through the strength check of the impeller, maximum equivalent stress of the three models was less than the allowable stress of the rotor material, which indicated the structural design of them met the safety requirement; (2) Through the critical speed check of the shafting rotor, the working speed of the VLSFP was lower than 0.8 times the first-order critical speed of the three models, which indicated the rotor could avoid the resonance and the structure of the three models met the dynamic design requirement. According to the stress check of the impeller and the critical speed check of the shafting rotor, combining the time and labor cost when the VLSFP was installed and disassembled many times before and after the test or operation, the paper selected the Z4 model to be the optimal model, which could provide a theoretical support for the subsequent structure design optimization of the vertical long shaft fire pump.

Nanoparticle-based drug delivery systems with platinum drugs for overcoming cancer drug resistance.

Platinum drugs are commonly used in cancer therapy, but their therapeutic outcomes have been significantly compromised by the drug resistance of cancer cells. To this end, intensive efforts have been made to develop nanoparticle-based drug delivery systems for platinum drugs, due to their multifunctionality in delivering drugs, in modulating the tumor microenvironment, and in integrating additional genes, proteins, and small molecules to overcome chemoresistance in cancers. To facilitate the clinical application of these promising nanoparticle-based platinum drug delivery systems, this paper summarizes the common mechanisms for chemoresistance towards platinum drugs, the advantages of nanoparticles in drug delivery, and recent strategies of nanoparticle-based platinum drug delivery. Furthermore, we discuss how to design delivery platforms more effectively to overcome chemoresistance in cancers, thereby improving the efficacy of platinum-based chemotherapy.

A greater lymph node yield is required during pathological examination in microsatellite instability-high gastric cancer.

BACKGROUND: The impact of microsatellite status on lymph node (LN) yield during lymphadenectomy and pathological examination has never been assessed in gastric cancer (GC). In this study, we aimed to appraise the association between microsatellite instability-high (MSI-H) and LN yield after curative gastrectomy. METHODS: We retrospectively analyzed 1757 patients with GC undergoing curative gastrectomy and divided them into two groups: MSI-H (n = 185(10.5%)) and microsatellite stability (MSS) (n = 1572(89.5%)), using a five-Bethesda-marker (NR-24, BAT-25, BAT-26, CAT-25, MONO-27) panel. The median LN count and the percentage of specimens with a minimum of 16 LNs (adequate LN ratio) were compared between the two groups. The log odds (LODDS) of positive LN count (PLNC) to negative LN count (NLNC) and the target LN examined threshold (TLNT(x%)) were calculated in both groups. RESULTS: Statistically significant differences were found in the median LN count between MSI-H and MSS groups for the complete cohort (30 vs. 28, p = 0.031), for patients undergoing distal gastrectomy (DG) (30 vs. 27, p = 0.002), for stage II patients undergoing DG (34 vs. 28, p = 0.005), and for LN-negative patients undergoing DG (28 vs. 24, p = 0.002). MSI-H was an independent factor for higher total LN count in patients undergoing DG (p = 0.011), but it was not statistically correlated to the adequate LN ratio. Statistically significant differences in PLNC, NLNC and LODDS were found between MSI-H GC and MSS GC (all p < 0.001). The TLNT(90%) for MSI-H and MSS groups were 31 and 25, respectively. TLNT(X%) of MSI-H GC was always higher than that of MSS GC regardless of the given value of X%. CONCLUSIONS: MSI-H was associated with higher LN yield in patients undergoing gastrectomy for GC. Although MSI-H did not affect the adequacy of LN harvest, we speculate that a greater lymph node yield is required during pathological examination in MSI-H GC.

Enhancing the chemotherapeutic efficacy of platinum prodrug nanoparticles and inhibiting cancer metastasis by targeting iron homeostasis.

Iron plays important roles in tumor growth and metastasis, and iron depletion has become a new therapeutic strategy for iron overload cancers. Cisplatin is widely applied in the clinical therapy of various malignancies, but it has no inhibitory effect on cancer metastasis. In the present study, we found that the combination of cisplatin and iron chelator Dp44mT resulted in enhanced cell apoptosis as well as attenuated cell mobility and migration in vitro. Next, we developed a nano-carrier system to promote intracellular drug accumulation and reduce the side effects in cancer cells. Results showed that the as-synthesized nanoparticles (NPs) exhibited excellent antitumor efficiency when combined with Dp44mT. In breast tumor-bearing mice, the combination of the NPs and Dp44mT dramatically prevented orthotopic mammary tumor growth and inhibited metastasis via downregulation of VEGFα, MMP2 and Vimentin. In conclusion, as a versatile nano-platform for the combination of chemotherapy and iron chelators, the current design holds great potential for metastasis-inhibited cancer therapy.

Author Correction: Nanoparticle conjugates of a highly potent toxin enhance safety and circumvent platinum resistance in ovarian cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Carboplatin prodrug conjugated Fe3O4 nanoparticles for magnetically targeted drug delivery in ovarian cancer cells.

Platinum (Pt)-based drugs including cisplatin, carboplatin and oxaliplatin have been widely used as first-line anticancer regimens due to their excellent anticancer efficacy. However, the clinical application of these drugs is greatly limited due to their side effects and drug resistance. In this study, an antitumor drug delivery system based on carboplatin prodrug loading Fe3O4 nanoparticles (NPs@carboplatin) was developed and the antitumor activity was also investigated. The as-synthesized NPs@carboplatin has an average diameter of 7.88 nm with a zeta potential of 8.11 mV. It exhibited a higher cytotoxic effect than carboplatin on both A2780 (cisplatin sensitive) and A2780DDP (cisplatin resistant) ovarian cancer cells via MTT assay, which can overcome Pt resistance. Moreover, the nanoparticles (NPs) loaded with carboplatin possess excellent delivery capability, which can be effectively taken up by ovarian cancer cell lines through an endocytosis process. With excellent delivery capability as carriers, NPs@carboplatin can promote drug internalization and result in the increase of intracellular drug accumulation with enhanced cellular cytotoxicity. Furthermore, in vivo experiments demonstrated that NPs@carboplatin can be widely distributed into major organs, and in the presence of an external magnetic field, the Fe3O4 nanocarrier is beneficial to visualize the tumor site location and promote the subsequent antitumor efficacy. It revealed a relatively high tumor inhibition rate without obvious potential toxicity to normal organs. Taken together, these results indicate that the magnetically targeted NPs@carboplatin can act as a drug delivery system and will have great potential in ovarian cancer therapeutic applications.

Differences in Nanoparticle Uptake in Transplanted and Autochthonous Models of Pancreatic Cancer.

Human pancreatic ductal adenocarcinoma (PDAC) contains a distinctively dense stroma that limits the accessibility of anticancer drugs, contributing to its poor overall prognosis. Nanoparticles can enhance drug delivery and retention in pancreatic tumors and have been utilized clinically for their treatment. In preclinical studies, various mouse models differentially recapitulate the microenvironmental features of human PDAC. Here, we demonstrate that through utilization of different organic cosolvents and by doping of a homopolymer of poly(ε-caprolactone), a diblock copolymer composition of poly(ethylene oxide)- block-poly(ε-caprolactone) may be utilized to generate biodegradable and nanoscale micelles with different physical properties. Noninvasive optical imaging was employed to examine the pharmacology and biodistribution of these various nanoparticle formulations in both allografted and autochthonous mouse models of PDAC. In contrast to the results reported with transplanted tumors, spherical micelles as large as 300 nm in diameter were found to extravasate in the autochthonous model, reaching a distance of approximately 20 µm from the nearest tumor cell clusters. A lipophilic platinum(IV) prodrug of oxaliplatin was further able to achieve a ∼7-fold higher peak accumulation and a ∼50-fold increase in its retention half-life in pancreatic tumors when delivered with 100 nm long worm-like micelles as when compared to the free drug formulation of oxaliplatin. Through further engineering of nanoparticle properties, as well as by widespread adoption of the autochthonous tumor model for preclinical testing, future therapeutic formulations may further enhance the targeting and penetration of anticancer agents to improve survival outcomes in PDAC.

Publisher Correction: Nanoparticle conjugates of a highly potent toxin enhance safety and circumvent platinum resistance in ovarian cancer.

The original version of this Article contained an error in the spelling of the author Yingjie Yu, which was incorrectly given as Yu Yingjie. Furthermore, in Figure 3a, the labels 'MD | p < 0.05' incorrectly read 'MD | p > 0.05'. These errors have now been corrected in both the PDF and HTML versions of the Article.

Nanoparticle conjugates of a highly potent toxin enhance safety and circumvent platinum resistance in ovarian cancer.

Advanced-stage epithelial ovarian cancers are amongst the most difficult to treat tumors and have proven to be refractory to most cytotoxic, molecularly targeted, or immunotherapeutic approaches. Here, we report that nanoparticle-drug conjugates (NDCs) of monomethyl auristatin E (MMAE) significantly increase loading on a per-vehicle basis as compared to antibody-drug conjugates (ADCs). Their intraperitoneal administration enabled triggered release of the active MMAE toxin to inhibit tumor growth and to extend animal survival to >90 days in a cell-line xenograft model of disseminated ovarian cancer. In a patient-derived xenograft model of advanced-stage and platinum-resistant ovarian cancer, an MMAE-based NDC doubled the duration of tumor growth inhibition as compared to cisplatin. NDCs of highly potent toxins thus introduce a translatable platform that may be exploited to maximize the safety and efficacy of cytotoxic chemotherapies, combining the best features of ADCs with those of nanoparticle-based therapeutics.

Early tumor detection afforded by in vivo imaging of near-infrared II fluorescence.

Cell-intrinsic reporters such as luciferase (LUC) and red fluorescent protein (RFP) have been commonly utilized in preclinical studies to image tumor growth and to monitor therapeutic responses. While extrinsic reporters that emit near infrared I (NIR-I: 650-950 nm) or near-infrared II (NIR-II: 1000-1700 nm) optical signals have enabled minimization of tissue autofluorescence and light scattering, it has remained unclear as to whether their use has afforded more accurate tumor imaging in small animals. Here, we developed a novel optical imaging construct comprised of rare earth lanthanide nanoparticles coated with biodegradable diblock copolymers and doped with organic fluorophores, generating NIR-I and NIR-II emissive bands upon optical excitation. Simultaneous injection of multiple spectrally-unique nanoparticles into mice bearing tumor implants established via intraperitoneal dissemination of LUC+/RFP+ OVCAR-8 ovarian cancer cells enabled direct comparisons of imaging with extrinsic vs. intrinsic reporters, NIR-II vs. NIR-I signals, as well as targeted vs. untargeted exogenous contrast agents in the same animal and over time. We discovered that in vivo optical imaging at NIR-II wavelengths facilitates more accurate detection of smaller and earlier tumor deposits, offering enhanced sensitivity, improved spatial contrast, and increased depths of tissue penetration as compared to imaging with visible or NIR-I fluorescent agents. Our work further highlights the hitherto underappreciated enhancements in tumor accumulation that may be achieved with intraperitoneal as opposed to intravenous administration of nanoparticles. Lastly, we found discrepancies in the fidelity of tumor uptake that could be obtained by utilizing small molecules for in vivo as opposed to in vitro targeting of nanoparticles to disseminated tumors.

Enhanced Cisplatin Chemotherapy by Iron Oxide Nanocarrier-Mediated Generation of Highly Toxic Reactive Oxygen Species.

Reactive oxygen species (ROS) plays a key role in therapeutic effects as well as side effects of platinum drugs. Cisplatin mediates activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), which triggers oxygen (O2) to superoxide radical (O2•-) and its downstream H2O2. Through the Fenton's reaction, H2O2 could be catalyzed by Fe2+/Fe3+ to the toxic hydroxyl radicals (•OH), which cause oxidative damages to lipids, proteins, and DNA. By taking the full advantage of Fenton's chemistry, we herein demonstrated tumor site-specific conversion of ROS generation induced by released cisplatin and Fe2+/Fe3+ from iron-oxide nanocarriers with cisplatin(IV) prodrugs for enhanced anticancer activity but minimized systemic toxicity.

Maximizing Synergistic Activity When Combining RNAi and Platinum-Based Anticancer Agents.

RNAi approaches have been widely combined with platinum-based anticancer agents to elucidate cellular responses and to target gene products that mediate acquired resistance. Recent work has demonstrated that platination of siRNA prior to transfection may negatively influence RNAi efficiency based on the position and sequence of its guanosine nucleosides. Here, we used detailed spectroscopic characterization to demonstrate rapid formation of Pt-guanosine adducts within 30 min after coincubation of oxaliplatin [OxaPt(II)] or cisplatin [CisPt(II)] with either guanosine monophosphate or B-cell lymphoma 2 (BCL-2) siRNA. After 3 h of exposure to these platinum(II) agents, >50% of BCL-2 siRNA transcripts were platinated and unable to effectively suppress mRNA levels. Platinum(IV) analogues [OxaPt(IV) or CisPt(IV)] did not form Pt-siRNA adducts but did display decreased in vitro uptake and reduced potency. To overcome these challenges, we utilized biodegradable methoxyl-poly(ethylene glycol)-block-poly(ε-caprolactone)-block-poly(l-lysine) (mPEG-b-PCL-b-PLL) to generate self-assembled micelles that covalently conjugated OxaPt(IV) and/or electrostatically complexed siRNA. We then compared multiple strategies by which to combine BCL-2 siRNA with either OxaPt(II) or OxaPt(IV). Overall, we determined that the concentrations of siRNA (nM) and platinum(II)-based anticancer agents (µM) that are typically used for in vitro experiments led to rapid Pt-siRNA adduct formation and ineffective RNAi. Coincorporation of BCL-2 siRNA and platinum(IV) analogues in a single micelle enabled maximal suppression of BCL-2 mRNA levels (to <10% of baseline), augmented the intracellular levels of platinum (by ∼4×) and the numbers of resultant Pt-DNA adducts (by >5×), increased the cellular fractions that underwent apoptosis (by ∼4×), and enhanced the in vitro antiproliferative activity of the corresponding platinum(II) agent (by 10-100×, depending on the cancer cell line). When combining RNAi and platinum-based anticancer agents, this generalizable strategy may be adopted to maximize synergy during screening or for therapeutic delivery.

Nanoparticle delivery of sterically hindered platinum(IV) prodrugs shows 100 times higher potency than that of cisplatin upon light activation.

The introduction of a sterically hindered pyridine ligand to a photosensitive platinum(iv) drug for drug delivery resulted in a >100 fold increase in effectiveness compared to the gold standard, cisplatin.