Molecular mechanisms targeting drug-resistance and metastasis in colorectal cancer: Updates and beyond.

Colorectal cancer (CRC) is the third most diagnosed malignancy and a major leading cause of cancer-related deaths worldwide. Despite advances in therapeutic regimens, the number of patients presenting with metastatic CRC (mCRC) is increasing due to resistance to therapy, conferred by a small population of cancer cells, known as cancer stem cells. Targeted therapies have been highly successful in prolonging the overall survival of patients with mCRC. Agents are being developed to target key molecules involved in drug-resistance and metastasis of CRC, and these include vascular endothelial growth factor, epidermal growth factor receptor, human epidermal growth factor receptor-2, mitogen-activated extracellular signal-regulated kinase, in addition to immune checkpoints. Currently, there are several ongoing clinical trials of newly developed targeted agents, which have shown considerable clinical efficacy and have improved the prognosis of patients who do not benefit from conventional chemotherapy. In this review, we highlight recent developments in the use of existing and novel targeted agents against drug-resistant CRC and mCRC. Furthermore, we discuss limitations and challenges associated with targeted therapy and strategies to combat intrinsic and acquired resistance to these therapies, in addition to the importance of implementing better preclinical models and the application of personalized therapy based on predictive biomarkers for treatment selection.

Novel therapeutic diiminoquinone exhibits anticancer effects on human colorectal cancer cells in two-dimensional and three-dimensional in vitro models.

BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality. Cancer stem cells (CSCs) in CRC, which are spared by many chemotherapeutics, have tumorigenic capacity and are believed to be the reason behind cancer relapse. So far, there have been no effective drugs to target colon CSCs. Diiminoquinone (DIQ) has shown promising effects on targeting colon cancer. However, there is limited research on the effects of DIQ on eradicating CSCs in CRC. AIM: To investigate the anticancer potential of DIQ on colon CSCs in two-dimensional (2D) and three-dimensional (3D) models using colonospheres and patient-derived organoids. METHODS: Various 2D methods have been used to assess the effect and the mechanism of DIQ on HCT116 and HT29 cell lines including cell proliferation and viability assays, migration and invasion assays, immunofluorescence staining, and flow cytometry. The potency of DIQ was also assessed in 3D culture using the sphere formation assay and colon cancer patient-derived organoid model. RESULTS: Our results showed that DIQ significantly inhibited cell proliferation, migration, and invasion in HCT116 and HT29 cell lines. DIQ treatment induced apoptosis along with an accumulation of HCT116 and HT29 cancer cells in the sub-G1 region and an increase in reactive oxygen species in both CRC cell lines. DIQ reduced sphere-forming and self-renewal ability of colon cancer HCT116 and HT29 stem/progenitor cells at sub-toxic doses of 1 µmol/L. Mechanistically, DIQ targets CSCs by downregulating the main components of stem cell-related -catenin, AKT, and ERK oncogenic signaling pathways. Potently, DIQ displayed a highly significant decrease in both the count and the size of the organoids derived from colon cancer patients as compared to control and 5-fluorouracil conditions. CONCLUSION: This study is the first documentation of the molecular mechanism of the novel anticancer therapeutic DIQ via targeting CSC, a promising compound that needs further investigation.

Thymoquinone Radiosensitizes Human Colorectal Cancer Cells in 2D and 3D Culture Models.

Resistance of cancer cells and normal tissue toxicity of ionizing radiation (IR) are known to limit the success of radiotherapy. There is growing interest in using IR with natural compounds to sensitize cancer cells and spare healthy tissues. Thymoquinone (TQ) was shown to radiosensitize several cancers, yet no studies have investigated its radiosensitizing effects on colorectal cancer (CRC). Here, we combined TQ with IR and determined its effects in two-dimensional (2D) and three-dimensional (3D) culture models derived from HCT116 and HT29 CRC cells, and in patient-derived organoids (PDOs). TQ sensitized CRC cells to IR and reduced cell viability and clonogenic survival and was non-toxic to non-tumorigenic intestinal cells. TQ sensitizing effects were associated with G2/M arrest and DNA damage as well as changes in key signaling molecules involved in this process. Combining a low dose of TQ (3 µM) with IR (2 Gy) inhibited sphere formation by 100% at generation 5 and this was associated with inhibition of stemness and DNA repair. These doses also led to ~1.4- to ~3.4-fold decrease in organoid forming ability of PDOs. Our findings show that combining TQ and IR could be a promising therapeutic strategy for eradicating CRC cells.

Comparing Emergent and Elective Colectomy Outcomes in Elderly Patients: A NSQIP Study.

INTRODUCTION: With the increasing prevalence of colorectal cancer (CRC) worldwide, especially in the elderly, and the variability between physiological and chronological age and its impact on functional status, acute symptoms leading to emergent surgery due to colorectal malignancy may lead to increased morbidity and mortality. The aim of this study is to identify the outcome differences of elective vs. emergent open colectomy in patients above 80 years. METHODS: The National Surgical Quality Improvement Program (NSQIP) database was reviewed from 2010 to 2014 for open colectomy based on CPT codes. Comparison between groups was done based on the clinical context at presentation as elective or emergent surgery. Data were analyzed using SAS. RESULTS: Elective colectomies were performed in 8289 (70.8%) vs. emergent colectomies in 3409 (29.1%). Emergent colectomy patients had higher American Society of Anesthesiologists (ASA) preoperative classification III-IV, 1429 (42.0%) and 224 (6.6%), vs. 1238 (14.9%) and 21 (0.2%) in elective colectomy patients (p < 0.0001). Emergent colectomy patients had more comorbidities such as chronic obstructive pulmonary disorder (493 (14.5%) vs. 796 (9.6%)), congestive heart failure (206 (6.0%) vs. 310 (3.8%)), dialysis (106 (3.1%) vs. 56 (0.7%)), and acute renal failure (166 (4.9%) vs. 46 (0.6%)) (p < 0.0001), respectively. Postoperative morbidity and mortality were significantly higher in emergent colectomy (1651 (48.4%) and 872 (25.6%)) vs. elective colectomy (1859 (22.4%) and 567 (6.8%)) (p < 0.0001), respectively. CONCLUSION: Emergent open colectomy in elderly patients carries a higher risk of morbidity and mortality when compared to elective open colectomy with risk factors being higher ASA classification and more comorbidities.

Potential role of micro ribonucleic acids in screening for anal cancer in human papilloma virus and human immunodeficiency virus related malignancies.

Despite advances in antiretroviral treatment (ART), human immunodeficiency virus (HIV) continues to be a major global public health issue owing to the increased mortality rates related to the prevalent oncogenic viruses among people living with HIV (PLWH). Human papillomavirus (HPV) is the most common sexually transmitted viral disease in both men and women worldwide. High-risk or oncogenic HPV types are associated with the development of HPV-related malignancies, including cervical, penile, and anal cancer, in addition to oral cancers. The incidence of anal squamous cell cancers is increasing among PLWH, necessitating the need for reliable screening methods in this population at risk. In fact, the currently used screening methods, including the Pap smear, are invasive and are neither sensitive nor specific. Investigators are interested in circulatory and tissue micro ribonucleic acids (miRNAs), as these small non-coding RNAs are ideal biomarkers for early detection and prognosis of cancer. Multiple miRNAs are deregulated during HIV and HPV infection and their deregulation contributes to the pathogenesis of disease. Here, we will review the molecular basis of HIV and HPV co-infections and focus on the pathogenesis and epidemiology of anal cancer in PLWH. The limitations of screening for anal cancer and the need for a reliable screening program that involves specific miRNAs with diagnostic and therapeutic values is also discussed.

MEBO versus topical Diltiazem versus a combination of both ointments in the treatment of acute anal fissure: a randomized clinical trial protocol.

BACKGROUND: Anal fissure is a common complication of the anorectal region and one of the most reported causes of anal pain. Acute anal fissure can be cured by surgery or medical treatment. There is an increase in the use of topical therapy for the treatment of anal fissures. A common topical drug used is Diltiazem (DTZ), a calcium-channel blocker, which relaxes the anal sphincter and thus promotes healing of the anal fissure. Moist exposed burn ointment (MEBO) is an ointment that is effective for the treatment of burns and wound healing and is becoming popular in the treatment of anal fissures. METHODS: This is a 1:1:1 randomized, controlled, parallel design, with endpoint measures of change in pain score, wound healing, defecation strain score and patient's global impression of improvement. The study will be conducted at AUBMC over a 10-week period. Patients will be randomized to three treatment arms: MEBO, Diltiazem, and a combination of MEBO and Diltiazem ointments. DISCUSSION: The results of this study will allow physicians to assess the efficacy and safety of MEBO in the treatment of acute anal fissure, and also in comparison to Diltiazem. This trial will generate evidence-based conclusions regarding the use of a herbal/natural-based product (MEBO ointment) for the treatment of anal fissures. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT04153032 . Clinical Trial Registration Date: 06-NOVEMBER-2019.

Presentation of intestinal malrotation and midgut volvulus in adults: Case report & literature review.

INTRODUCTION: Malrotation is considered a newborn disease. This case report sheds light on the rare, but possible late presentation of malrotation in adulthood, which if missed, can leave the patient in a detrimental state. PRESENTATION OF CASE: 28-year-old female presented in critical state with acute abdomen. Computed tomography abdomen/pelvis showed midgut volvulus, requiring urgent laparotomy. The patient's bowels were discolored, yet they normalized upon detorsion, except for a small portion, which was equivocal and left for observation. Ladd's bands were excised, and the abdomen was closed with Bogota bag for re-exploration. The patient underwent two more laparotomies to observe the intestinal segment until it was back to normal. Ladd procedure was then completed, and an absorbable mesh was applied. Follow-up of 20 months has been uneventful, except for a small, asymptomatic, incisional hernia. DISCUSSION: Malrotation in adults is often missed due to its subacute, nonspecific presentation. It is often diagnosed by CT abdomen, which shows inversion or vertical positioning of the superior mesenteric vessels. Symptomatic, but stable patients, can undergo laparoscopic Ladd procedure, which carries the benefit of less length of stay. While an incidental malrotation can be prophylactically operated on, correcting asymptomatic malrotation beyond age of 20 is ineffective and possibly harmful. CONCLUSION: Intestinal malrotation presenting in an adult should be on the differential diagnosis when dealing with abdominal pain, especially in the context of small bowel obstruction in a virgin abdomen. It is vital to consider a patient's age prior to prophylactically operate on malrotation discovered incidentally.

Recurrent Acute Diverticulitis: When to Operate?

OBJECTIVE: Recurrent acute diverticulitis carries a major burden to any form of health care. Patients present repeatedly to medical centers with a multitude of symptoms and may require different modalities of treatment with significant morbidities and impact on quality of life. METHODS: We therefore wanted to identify factors that would imply the need and time of surgery versus conservative management. The literature was thoroughly searched for major studies tackling this topic. Furthermore, studies reporting on decision making based on quality of life were included. Risks of developing recurrent diverticulitis and the potential need of surgery were identified. Relevant surgical details that would decrease recurrence were also denoted. RESULTS: Surgery has been the mainstay of treatment for quite some time. However, the paradigms of treatment have changed over the last few years, especially when long-term population studies confirmed that not all patients require surgical treatment with its associated risk of morbidity. CONCLUSION: Treatment now has to be patient-tailored with special attention to the subgroup of high-risk patients. These patients must be adequately selected, identifying the impact of the disease on the quality of life and weighing in the risks of the surgical intervention.

Inorganic Nanoparticles as Donors in Resonance Energy Transfer for Solid-Phase Bioassays and Biosensors.

Bioassays for the rapid detection and quantification of specific nucleic acids, proteins, and peptides are fundamental tools in many clinical settings. Traditional optical emission methods have focused on the use of molecular dyes as labels to track selective binding interactions and as probes that are sensitive to environmental changes. Such dyes can offer good detection limits based on brightness but typically have broad emission bands and suffer from time-dependent photobleaching. Inorganic nanoparticles such as quantum dots and upconversion nanoparticles are photostable over prolonged exposure to excitation radiation and tend to offer narrow emission bands, providing a greater opportunity for multiwavelength multiplexing. Importantly, in contrast to molecular dyes, nanoparticles offer substantial surface area and can serve as platforms to carry a large number of conjugated molecules. The surface chemistry of inorganic nanoparticles offers both challenges and opportunities for the control of solubility and functionality for selective molecular interactions by the assembly of coatings through coordination chemistry. This report reviews advances in the compositional design and methods of conjugation of inorganic quantum dots and upconversion nanoparticles and the assembly of combinations of nanoparticles to achieve energy exchange. Our interest is the exploration of configurations where the modified nanoparticles can be immobilized to solid substrates for the development of bioassays and biosensors that operate by resonance energy transfer (RET).

Resonance Energy Transfer-Based Nucleic Acid Hybridization Assays on Paper-Based Platforms Using Emissive Nanoparticles as Donors.

Quantum dots (QDs) and upconverting nanoparticles (UCNPs) are luminescent nanoparticles (NPs) commonly used in bioassays and biosensors as resonance energy transfer (RET) donors. The narrow and tunable emissions of both QDs and UCNPs make them versatile RET donors that can be paired with a wide range of acceptors. Ratiometric signal processing that compares donor and acceptor emission in RET-based transduction offers improved precision, as it accounts for fluctuations in the absolute photoluminescence (PL) intensities of the donor and acceptor that can result from experimental and instrumental variations. Immobilizing NPs on a solid support avoids problems such as those that can arise with their aggregation in solution, and allows for facile layer-by-layer assembly of the interfacial chemistry. Paper is an attractive solid support for the development of point-of-care diagnostic assays given its ubiquity, low-cost, and intrinsic fluid transport by capillary action. Integration of nanomaterials with paper-based analytical devices (PADs) provides avenues to augment the analytical performance of PADs, given the unique optoelectronic properties of nanomaterials. Herein, we describe methodology for the development of PADs using QDs and UCNPs as RET donors for optical transduction of nucleic acid hybridization. Immobilization of green-emitting QDs (gQDs) on imidazole functionalized cellulose paper is described for use as RET donors with Cy3 molecular dye as acceptors for the detection of SMN1 gene fragment. We also describe the covalent immobilization of blue-emitting UCNPs on aldehyde modified cellulose paper for use as RET donors with orange-emitting QDs (oQDs) as acceptors for the detection of HPRT1 gene fragment. The data described herein is acquired using an epifluorescence microscope, and can also be collected using technology such as a typical electronic camera.

A paper-based multiplexed resonance energy transfer nucleic acid hybridization assay using a single form of upconversion nanoparticle as donor and three quantum dots as acceptors.

Monodisperse aqueous upconverting nanoparticles (UCNPs) were covalently immobilized on aldehyde modified cellulose paper via reductive amination to evaluate the multiplexing capacity of luminescence resonance energy transfer (LRET) between UCNPs and quantum dots (QDs). This is the first account of a multiplexed bioassay strategy that demonstrates the principle of use of a single form of UCNP as donor and three different color emitting QDs as acceptors to concurrently determine three analytes. Broad absorbance profiles of green, orange and red QDs that spanned from the first exciton absorption peak to the UV region were in overlap with a blue emission band from UCNPs composed of NaYF4 that was doped with 30% Yb3+, 0.5% Tm3+, allowing for LRET that was stimulated using 980 nm near-infrared radiation. The characteristic narrow and well-defined emission peaks of UCNPs and QDs allowed for the collection of luminescence from each nanoparticle using a band-pass optical filter and an epi-fluorescence microscope. The LRET system was used for the concurrent detection of uidA, Stx1A and tetA gene fragments with selectivity even in serum samples, and reached limits of detection of 26 fmol, 56 fmol and 76 fmol, respectively.

The forgotten biliary stent: an unusual cause of diarrhea.

This case highlights the possible complications of biliary stents, which may include migration and impaction in the gastrointestinal tract. It also emphasizes the need for a robust follow-up system after stent placement, to minimize the risks and possible sequelae of a forgotten stent.

Colonoscopy without sedation: Patient factors alone are less likely to influence its uptake.

BACKGROUND AND STUDY AIMS: Conscious sedation during colonoscopy minimizes discomfort, improves polyp detection rates, and reduces technical failure, but carries medication-related risks and requires dedicated and costly recovery services. Sedation-free procedures may offer a safer alternative. We aimed to compare this group with those receiving sedation to determine differences in patient characteristics, cecal intubation rates, polyp detection rates, discomfort levels and safety in patients for whom anesthesia is high risk. PATIENTS AND METHODS: Prospectively collected data from all colonoscopies performed over a 1-year period at three district general hospitals were analyzed. Conscious sedation was offered to all patients and outcomes in those who refused were compared with outcomes in those who received sedation. RESULTS: One hundred ninety-four of 1694 (11 %) colonoscopies were performed without sedation (61 % male, P < 0.001) but rates varied between hospitals. Of these, 55 % were American Society of Anesthesiologists (ASA) grade 3 or more and 5 % experienced moderate discomfort, compared to 40 % (P < 0.0001) and 10 % (P = 0.023) respectively of those receiving sedation. They were more likely to have indications of rectal bleeding or frequency of stool and less likely to have anaemia or macroscopic inflammation at colonoscopy. Complications, completion. and polyp detection rates were similar in both groups. CONCLUSIONS: Colonoscopy without sedation can be completed successfully in select patients without compromising comfort or polyp detection rates and is safe in those for whom anesthesia is high risk. It is therefore a safe alternative for clinicians concerned about sedation, but the findings suggest that hospital, rather than patient factors, may prevent its uptake.

Utilisation of the falciform ligament pedicle flap as an alternative approach for the repair of a perforated gastric ulcer.

An 83-year-old woman presented to the emergency department with sudden onset of severe abdominal pain. She had a background of ulcerative colitis managed surgically at the age of 18 years with panproctocolectomy and permanent ileostomy. On admission, clinical assessment suggested a visceral perforation and an urgent CT scan demonstrated a perforated prepyloric ulcer. Emergency laparotomy was performed and confirmed a 3 cm perforated pre-pyloric ulcer. Repair of the defect was challenging due to the absence of omental fat to patch the perforation. A modification to the standard technique was therefore performed: the falciform ligament was mobilised and its free end used as a patch to repair the defect. The patient made a good postoperative recovery. This case report highlights an alternative operative technique for the treatment of perforated gastric/duodenal ulcers in patients who lack omentum, or when omentum cannot be used to cover perforated gastroduodenal ulcers.

Laparoscopic 'sleeve' caecectomy for idiopathic solitary caecal ulcer mimicking appendicitis.

Idiopathic ulcer of the caecum is a rare condition of unknown aetiology. Its clinical presentation may mimic various pathologies, including appendicitis, inflammatory bowel disease and caecal malignancy. A definitive diagnosis is rarely established preoperatively, and is usually only confirmed histologically following surgical resection. We report a case of a young patient with caecal ulceration presenting with symptoms and signs of appendicitis, in whom laparoscopic anterior 'sleeve' caecectomy was performed to excise an inflammatory-looking mass involving the caecum. Histological examination demonstrated a deep mucosal ulcer and subsequent colonoscopy did not reveal any further pathology.

Implementing a Pro-forma for Multidisciplinary Management of an Enterocutaneous Fistula: A Case Study.

Optimal management of patients with an entercocutaneous fistula (ECF) requires utilization of the sepsis, nutrition, anatomy, and surgical procedure (SNAP) protocol. The protocol includes early detection and treatment of sepsis, optimizing patient nutrition through oral and parenteral routes, identifying the fistula anatomy, optimal fistula management, and proceeding to corrective surgery when appropriate. The protocol requires multidisciplinary team (MDT) coordination among surgeons, nurses, dietitians, stoma nurses, and physiotherapists. This case study describes a 70-year-old man who developed an ECF subsequent to a laparotomy for a small bowel obstruction. Following a period of ileus, 16 days post laparotomy the patient developed a high-output (2,000 mL per day) fistula. The patient also became pyrexial with raised inflammatory markers, requiring antibiotic treatment. Following development of his ECF, he was managed using the SNAP protocol for the duration of his admission; however, in implementing this protocol with this patient, clinicians noted fluid charts were inadequate to allow effective management of the variables. Thus, a new pro-forma was created that encompassed fluid balance, nutritional status, and pertinent blood test results, as well as perifistular skin condition, medication, and documentation of management plans from the MDT team. The pro-forma was recorded daily in the patient notes. Following implementation of the pro-forma and the SNAP protocol, the patient recovered well clinically over a period of 4 weeks with a decrease in his fistula output to 300-500 mL per day, and he was discharged with plans for further corrective surgery to resect the fistula and for bowel re-anastomoses. Although fluid charts are readily available, they do not include all pertinent variables for optimal management of patients with an ECF. Further research is needed to validate the pro-forma and evaluate its effect on patient outcomes.

A paper-based resonance energy transfer nucleic acid hybridization assay using upconversion nanoparticles as donors and quantum dots as acceptors.

Monodisperse aqueous upconverting nanoparticles (UCNPs) were covalently immobilized on aldehyde modified cellulose paper via reduction amination to develop a luminescence resonance energy transfer (LRET)-based nucleic acid hybridization assay. This first account of covalent immobilization of UCNPs on paper for a bioassay reports an optically responsive method that is sensitive, reproducible and robust. The immobilized UCNPs were decorated with oligonucleotide probes to capture HPRT1 housekeeping gene fragments, which in turn brought reporter conjugated quantum dots (QDs) in close proximity to the UCNPs for LRET. This sandwich assay could detect unlabeled oligonucleotide target, and had a limit of detection of 13 fmol and a dynamic range spanning nearly 3 orders of magnitude. The use of QDs, which are excellent LRET acceptors, demonstrated improved sensitivity, limit of detection, dynamic range and selectivity compared to similar assays that have used molecular fluorophores as acceptors. The selectivity of the assay was attributed to the decoration of the QDs with polyethylene glycol to eliminate non-specific adsorption. The kinetics of hybridization were determined to be diffusion limited and full signal development occurred within 3 min.

Portomesenteric venous gas: A late complication of pneumatosis intestinalis.

BACKGROUND: The pneumatosis intestinalis is an entity with multiple aetiologies and may be associated with a fatal outcome when present on plain radiographs. When associated with the presence of portomesenteric venous gas (PMVG) it is typically the result of bowel ischaemia. METHODS AND RESULTS: We are presenting a case of a 43 year old male who presented with a two days history of haematemesis, generalised abdominal pain and distension. Computed tomography (CT) scan revealed a gross amount of air within the portal venous system and small bowel dilatation to the level of distal ileum was also seen with associated pneumatosis intestinalis. Emergency laparotomy was conducted which demonstrated a simple band adhesion resulting in bowel ischaemia. The patient was making a good post-operative recovery complicated only by sub-therapeutic treatment of schizophrenia. CONCLUSION: The presence of gas within the portal venous system and PI in adults can indicate severe life-threatening disease. This requires early surgical intervention in those patients with a clinical suspicion of bowel ischaemia, and with radiological signs. This may avoid significant mortality.

The intersection of CMOS microsystems and upconversion nanoparticles for luminescence bioimaging and bioassays.

Organic fluorophores and quantum dots are ubiquitous as contrast agents for bio-imaging and as labels in bioassays to enable the detection of biological targets and processes. Upconversion nanoparticles (UCNPs) offer a different set of opportunities as labels in bioassays and for bioimaging. UCNPs are excited at near-infrared (NIR) wavelengths where biological molecules are optically transparent, and their luminesce in the visible and ultraviolet (UV) wavelength range is suitable for detection using complementary metal-oxide-semiconductor (CMOS) technology. These nanoparticles provide multiple sharp emission bands, long lifetimes, tunable emission, high photostability, and low cytotoxicity, which render them particularly useful for bio-imaging applications and multiplexed bioassays. This paper surveys several key concepts surrounding upconversion nanoparticles and the systems that detect and process the corresponding luminescence signals. The principle of photon upconversion, tuning of emission wavelengths, UCNP bioassays, and UCNP time-resolved techniques are described. Electronic readout systems for signal detection and processing suitable for UCNP luminescence using CMOS technology are discussed. This includes recent progress in miniaturized detectors, integrated spectral sensing, and high-precision time-domain circuits. Emphasis is placed on the physical attributes of UCNPs that map strongly to the technical features that CMOS devices excel in delivering, exploring the interoperability between the two technologies.

Near-infrared-triggered anticancer drug release from upconverting nanoparticles.

Targeted drug delivery using functional nanoparticles has provided new strategies for improving therapeutic efficacy while concurrently minimizing toxicity. Photodynamic therapy is an approach that offers control of drug delivery by use of an external photon source to allow active therapeutic release to a target area. Upconverting nanoparticles (UCNPs) have potential to operate as integral components of photodynamic therapeutic platforms based on the resonant absorption of near-infrared (NIR) radiation and emission at shorter wavelengths. NIR radiation is minimally absorbed and scattered by biological tissues, and the NIR excitation of UCNPs can generate anti-Stokes emission in the ultraviolet-visible wavelength range at intensities that can be used to trigger cleavage of bonds linking therapeutics at the nanoparticle interface. Herein, we describe an investigation of photocleavage at the surface of UCNPs to release the chemotherapeutic 5-fluorouracil (5-FU). Core-shell UCNPs composed of a ß-NaYF4: 4.95% Yb, 0.08% Tm core and a ß-NaYF4 shell were coated with o-phosphorylethanolamine ligands and coupled to an o-nitrobenzyl (ONB) derivative of 5-FU. NIR excitation of the UCNPs resulted in photoluminescence (PL) emission bands centered at 365, 455, and 485 nm. The UV-blue PL was in resonance with the absorption band of the ONB-FU derivative resulting in photocleavage and subsequent release of the 5-FU drug from the UCNPs for these in vitro studies. The release of 5-FU was complete in <14 min using a NIR laser source centered at 980 nm that operated at a power of <100 mW. The efficiency of triggered release was as high as 77% of the total ONB-FU conjugate, while the rate of drug release could be tuned with the laser power output. This work provides an important first step in the development of a UCNP platform capable of targeted chemotherapy.