Chemotherapy is a powerful cancer treatment but suffers from poor biocompatibility and a lack of tumor targeting. Here, we developed a CD44-targeted polymeric nanocomplex by encapsulating 10-hydroxycamptothecin (HCPT) into hyaluronic acid nanoparticles (HANP) for targeted cancer therapy. In vitro, theHANP/HCPT showed improved cytotoxicity to five cancer cell lines including HT29, A549,MDA-MB-231,HepG2, andMDA-MB-435 versus freeHCPT.After systemic administration into MDA-MB- 231 breast cancer xenograft, tumor growth was significantly inhibited 5.25 ± 0.21 times in the HANP/HCPT treated group relative to the nontreated group. In addition, the treatment response was also accessed and confirmed by 18F-fluoro-2-deoxy-D-glucose ([18F] FDG) positron emission tomography (PET). The MDA-MB-231 tumors responded to HANP/HCPT 7 days after the first treatment, which benefits treatment strategy adjustment and personalization. No apparent systemic toxic effects were seen in mice treated with HANP/HCPT. In summary, the HANPs have great promise as a targeted drug carrier for cancer chemotherapy. Our HANP platform can also deliver other hydrophobic chemotherapy agents.

Phototherapy is a light-triggered treatment for tumor ablation and growth inhibition via photodynamic therapy (PDT) and photothermal therapy (PTT). Despite extensive studies in this area, a major challenge is the lack of selective and effective phototherapy agents that can specifically accumulate in tumors to reach a therapeutic concentration. Although recent attempts have produced photosensitizers complexed with photothermal nanomaterials, the tedious preparation steps and poor tumor efficiency of therapy still hampers the broad utilization of these nanocarriers. Herein, we developed a CD44 targeted photoacoustic (PA) nanophototherapy agent by conjugating Indocyanine Green (ICG) to hyaluronic acid nanoparticles (HANPs) encapsulated with single-walled carbon nanotubes (SWCNTs), resulting in a theranostic nanocomplex of ICG-HANP/SWCNTs (IHANPT). We fully characterized its physical features as well as PA imaging and photothermal and photodynamic therapy properties in vitro and in vivo. Systemic delivery of IHANPT theranostic nanoparticles led to the accumulation of the targeted nanoparticles in tumors in a human cancer xenograft model in nude mice. PA imaging confirmed targeted delivery of the IHANPT nanoparticles into tumors (T/M ratio = 5.19 ± 0.3). The effect of phototherapy was demonstrated by low-power laser irradiation (808 nm, 0.8 W/cm2) to induce efficient photodynamic effect from ICG dye. The photothermal effect from the ICG and SWCNTs rapidly raised the tumor temperature to 55.4 ± 1.8 °C. As the result, significant tumor growth inhibition and marked induction of tumor cell death and necrosis were observed in the tumors in the tumors. There were no apparent systemic and local toxic effects found in the mice. The dynamic thermal stability of IHANPT was studied to ensure that PTT does not affect ICG-dependent PDT in phototherapy. Therefore, our results highlight imaging property and therapeutic effect of the novel IHANPT theranostic nanoparticle for CD44 targeted and PA image-guided dual PTT and PDT cancer therapy.

This special issue is dedicated to theranostic studies including original research articles and review articles, which integrate specialized diagnosis and therapy using the various theranostic probes with an emphasis on cancer research. The new term “theranostics” was coined by combining two words: therapeutic and diagnostic. More specifically, therapeutic strategies including photodynamics, chemotherapy, gene therapy, hyperthermia, and radiation are integrated with one or more diagnostic imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI), position emission tomography (PET), single photon emission computed tomography (SPECT), near-infrared (NIR) fluorescence imaging, and ultrasonography to develop molecular diagnostic tests and targeted therapeutics in clinics, resulting in the advance of personalized medicine. Therefore, these cutting-edge technologies allow us to simultaneously diagnose, image, and treat cancer and monitor the response of cancer treatment.

Despite current advances in new approaches for cancer detection and treatment, pancreatic cancer remains one of the most lethal cancer types. Difficult to detect early, aggressive tumor biology, and resistance to chemotherapy, radiotherapy, and immunotherapy result in a poor prognosis of pancreatic cancer patients with a 5-year survival of 10%. With advances in cancer nanotechnology, new imaging and drug delivery approaches that allow the development of multifunctional nanotheranostic agents offer opportunities for improving pancreatic cancer treatment using precision oncology. In this review, we will introduce potential applications of innovative theranostic strategies to address major challenges in the treatment of pancreatic cancer at different disease stages. Several important issues concerning targeted delivery of theranostic nanoparticles and tumor stromal barriers are discussed. We then focus on the development of a magnetic iron oxide nanoparticle platform for multimodal therapy of pancreatic cancer, including MRI monitoring targeted nanoparticle/drug delivery, therapeutic response, and tumor re-staging, activation of tumor immune response by immunoactivating nanoparticle and magnetic hyperthermia therapy, and intraoperative interventions for improving the outcome of targeted therapy. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.