Editorial: Nanoscale approaches for cancer diagnosis and treatment

The past decade has witnessed tremendous progress in the area of nanobiotechnology and nanomedicine. In particular, numerous research efforts have explored innovative nanotechnology approaches for ex vivo diagnosis, in vivo imaging, and in vivo treatment of cancer, offering encouraging results in preclinical animal studies. Clinical translation of some of these products is in progress. The guest editors of this themed issue “Nanoscale approaches for cancer diagnosis and treatment” were responsible for inviting the authors to submit manuscripts for inclusion in the publication. All manuscripts were handled by the editorial office of Nanoscale. The papers highlight recent advances in diverse areas of nanotechnology strategies for cancer diagnosis and therapy.

This special issue contains eight full and mini-review articles summarizing innovative approaches to design and fabricate functional nanomaterials, the applications of different types of nanoparticles for cancer nanotechnology, as well as some specific fundamental problems in this field of study. Jiang et al. (DOI: 10.1039/C5NR07964K) summarized recent advances in the use of microfluidic devices to fabricate drug-loaded polymeric nanoparticles. Compared with conventional methods to synthesize nanoparticles, this method enables more precise control of the nanoparticle size, composition, surface modification, structure and rigidity. The mini-review by Zhao et al. (DOI: 10.1039/C5NR07853A) described different types of silica-based hybrid nanosystems, including silica–metallic, silica–gold, silica–quantum dot, silica–upconversion, silica–carbon, and organosilica hybrid nanoparticles. Applications of these multifunctional nanomaterials in cancer imaging and treatment were discussed. Multifunctionality is an important attribute that distinguishes nanoparticles from many small molecules. In this regard, Pang et al. provided a comprehensive review (DOI: 10.1039/C5NR08534A) on the development of fluorescent/magnetic micro/nano-spheres based on quantum dots and/or magnetic nanoparticles for separating and enriching cancer cells from ex vivo samples, cancer imaging and diagnosis, as well as different types of cancer therapies. Furthermore, Dai et al. (DOI: 10.1039/C5NR07849K) reviewed the synthesis of porphyrin-loaded nanoparticles and their applications for cancer theranostics. Various functional components including targeting, imaging and therapeutic functions could be easily integrated into a single nanoparticle platform for these porphyrin-loaded nanoparticles.

In addition to the above reviews focusing on different types of nanoparticles, a number of other reviews and mini-reviews discussed specific issues in cancer nanotechnology. Kim et al., in their mini-review (DOI: 10.1039/C5NR05264E), described the pharmacokinetics, pharmacodynamics and toxicology of theranostic nanoparticles. It is believed that the physicochemical properties of nanoparticles are critically important for their future clinical use. The therapeutic applications of anti-angiogenic nanomaterials for cancer treatment were discussed by Patra et al., (DOI: 10.1039/C5NR07887C). Anti-angiogenic therapy using various nanoparticle-based drug/gene/peptide delivery systems could be a useful alternative treatment approach for cancer compared to traditional chemotherapy and radiation therapy. Another interesting review paper by Choyke et al. (DOI: 10.1039/C5NR05552K) introduced a new paradigm in enhanced permeation and retention effects, termed ‘super enhanced permeability and retention’ (SUPR) effects in tumors after near infrared (NIR) light triggered photoimmunotherapy. If the SUPR effect is validated under diverse conditions, it will allow remarkably enhanced passive tumor homing of nanoparticles – much better than that achieved with the conventional enhanced permeability and retention (EPR) effect. In addition, Hasan et al. contributed a comprehensive review article about nanotechnology-based photodynamic therapy, or so called photonanomedicine (PNM) in their article (DOI: 10.1039/C5NR08691D). Different PNM formulations as well as their potential for clinical translation have been discussed in this review.

This themed issue also includes 19 original research articles, most of which are focused on the development of nanoscale platforms for cancer imaging and therapy. Before biomedical applications of nano-agents, their surface modification is an essential first step in most cases. Two of the reports studied surface engineering of nanomaterials for biomedical applications. In a study by Kim and co-workers (DOI: 10.1039/C5NR08686H), a fluorescent derivative of a beta-lactam antibiotic, ampicillin (iAmp) was found to be a biocompatible shielding agent to functionalize theranostic nanomaterials such as carbon nanotubes (CNTs). These iAmp coated CNTs showed impressive physiological stability, minimal non-specific protein adsorption on their surface, and relative inertness to immune cells. A different study by Wang and co-workers (DOI: 10.1039/C6NR00649C) revealed that nanostructures could amplify the effect of surface charge on cell adhesion. Their findings could be useful to guide the design of new biomedical materials with tailored cell adhesion for applications in tissue implantation and regeneration.

Optical imaging techniques have been extensively applied in biomedicine research for decades. However, newer hybrid imaging platforms such as photoacoustic imaging have recently stimulated interest in the use of light-absorbing nanomaterials to overcome challenges associated with conventional optical imaging techniques. For example, Wang's group (DOI: 10.1039/C6NR00060F) reported the use of indocyanine green (ICG)-loaded Ag₂S nanoparticles for dual modal photoacoustic and second window NIR (NIR-II) fluorescence imaging. Using this nano-probe, they successfully demonstrated in vivo imaging of atherosclerosis in a mouse model. In another work by the Zheng group (DOI: 10.1039/C5NR08165C), nanoscale J-aggregates were exploited for in vivo fluorescence and photoacoustic imaging. They demonstrated real-time intraoperative detection of metastatic lymph nodes in a rabbit head-and-neck cancer model. Beyond fluorescence and photoacoustic imaging, upconversion luminescence imaging has also shown great promise in biomedical imaging owing to the rather low auto-fluorescence background and high signal-to-noise ratio. Gao and co-workers (DOI: 10.1039/C5NR07858J) developed NaGdF₄:Yb,Er@NaGdF₄ co-shell upconversion luminescence nanoparticles with a polyethylene glycol (PEG) coating and folic acid conjugation. Application of these nanoparticles in the optical imaging of primary colorectal tumors allowed the detection of cancer with high sensitivity in the complex abdominal environment.

Magnetic resonance (MR) imaging is a widely used medical imaging technique in the clinic. Three of the research papers focused on the development of nano-probes for MR imaging. Yang and co-workers (DOI: 10.1039/C5NR09071G) engineered a novel type of Gd³⁺-binding protein that specifically targets prostate-specific membrane antigen (PSMA). Using both T₁ and T₂-weighted MR imaging with a 7-T MR scanner, they successfully determined PSMA expression levels in tumors using mice. In another work by Lee et al. (DOI: 10.1039/C5NR06542A), Fe₃O₄-loaded pH-responsive biodegradable polymeric micelles were fabricated. Owing to the pH-dependent switching of micelle structures, the T₂-weighted MR signals of those nano-probes would be changed, enabling diagnostic imaging of acidic pathological tissues, such as the cerebral ischemic area. To overcome the inherent limitations of single-modal imaging, the Cai group (DOI: 10.1039/C5NR09193D) labeled reduced graphene oxide–iron oxide nanoparticles with radio-isotope ⁶⁴Cu for multimodal positron emission tomography (PET), photoacoustic, and MR imaging. With a long blood circulation half-life, the nano-probe could efficiently target tumors to allow multimodal tumor imaging in a mouse breast cancer tumor model.

Another major direction in the nanomedicine field is nanoscale delivery systems for cancer therapy. To accomplish this goal, the Tang group (DOI: 10.1039/C5NR08782A) reported a highly fluorescence aggregation-induced-emission (AIE)-active nano-agent for cell imaging and drug delivery. The work demonstrated the feasibility of killing breast cancer cells by this approach. Minimizing off-target toxicity is an important challenge in chemotherapy. The prodrug design is an effective approach in solving this problem. In this regard, Shuai and co-workers (DOI: 10.1039/C5NR07868G) synthesized a doxorubicin (DOX) prodrug containing copolymer and used it to construct hollow nano-vehicles in which hydrophilic drugs such as DOX·HCl and arsenite were encapsulated. Through the incorporation of a pH dual-sensitive hydrophobic membrane in this nanostructure, rapid release of physically entrapped DOX·HCl and arsenite inside acidic lysosomes was achieved. Additional enhancement of the localized therapeutic effect was achieved when the redox-sensitive DOX conjugate was reduced inside the cytosol in the presence of glutathione was observed, contributing to the enhanced therapeutic effect on DOX-resistant tumor cells. Beyond organic nanoparticles, SiO₂ based self-decomposable nanoparticles were fabricated by Li and co-workers (DOI: 10.1039/C5NR06305A) and used to load different types of drugs simultaneously. These nano-constructs improved drug efficacy and reduced system toxicity in their animal studies. Taking advantage of the photochemical internalization (PCI) mechanism, Qu et al. (DOI: 10.1039/C5NR07719B) developed graphitic hollow carbon nitride nanospheres, which could simultaneously act as a photosensitizer and a drug carrier. The light-triggered disruption of endosomes with this nano-carrier enabled enhanced therapeutic potency and specificity against cancer cells.

In addition to the delivery of chemotherapeutics, delivery of genetic agents or radioisotopes for gene therapy or radiation therapy of cancers, respectively, were also reported. Howard et al. (DOI: 10.1039/C5NR07206A) presented a mucosal design-based system for local delivery of oligonucleotides, achieving effective gene silencing which is promising for the treatment of mucosal tumors. In a series of in vitro studies, Bianco et al. (DOI: 10.1039/C5NR07923C) synthesized antibody-functionalized carbon nanotubes filled with radioactivatable metals for epidermal growth factor receptor (EGFR)-targeted cancer therapy.

The use of NIR light, magnetic fields, or ultrasound to increase local tumor temperature for hyperthermia therapy of cancer with the help of nano-agents has become an active field of study in recent years. The Lin group (DOI: 10.1039/C5NR06322A) fabricated Cu₉S₅@mSiO₂@Fe₃O₄-PEG multi-component nanoparticles and loaded them with anti-cancer drug DOX for combined MR imaging and chemo/photothermal synergistic therapy. The therapeutic outcome of such therapy could be further improved if a magnetic field was locally applied in the tumor to enhance the tumor accumulation of those nanoparticles. Another work by Chan et al. (DOI: 10.1039/C5NR08463F) revealed that a photothermal effect within a collagen matrix could greatly enhance the diffusion of nanoparticles inside tumor stroma, potentially allowing high accumulation of these agents in tumors to improve cancer therapeutic or diagnostic outcome. Other therapeutic nanocarriers were also discussed. For example, Chen et al. (DOI: 10.1039/C5NR07782F) developed unique nanocomposites by incorporating mesoporous silica coated reduced nano-graphene oxide with iron oxide nanoparticles (nrGO@MSN-ION) as nanocarriers, which could be employed to enhance the therapeutic effect of combined sonodynamic therapy & ultrasound hyperthermia therapy in killing tumors under the guidance of MR imaging. This sound-triggered therapy offers greatly improved tissue penetration compared to photothermal therapy induced by NIR light.

Finally, several other reports addressed interesting fundamental issues in the field of cancer nanomedicine. It is known that the acidic tumor microenvironment can potentiate tumor aggressiveness and metastasis. Som et al. (DOI: 10.1039/C5NR06162H) demonstrated that calcium carbonate nanoparticles (nano-CaCO₃) were able to increase and maintain the pH of tumors at 7.4, a condition that significantly delayed the tumor growth. This strategy may be combined with other conventional cancer treatment methods to optimize therapeutic benefits. Considering the wide clinical use of albumin-bound-paclitaxel nanoparticles (trade name Abraxane®), Godin et al. (DOI: 10.1039/C5NR07796F) conducted a careful study to understand the role of macrophages in the transport of these nanoparticles using in vitro, in vivo, and in silico evaluations. Based on the detected macrophage levels in tumors, the combined experimental/computational approach the authors described may be useful in predicting the performance of albumin-bound-paclitaxel to treat metastatic cancer.

In summary, this themed issue covers different research directions in the field of cancer nanotechnology, including syntheses and surface engineering strategies for biomedical nanomaterials, the development of nanoparticles as biomedical imaging probes, and the uncovering of new nanoscale platforms for drug delivery and cancer theranostics. It is hoped that this themed issue on “Nanoscale approaches for cancer diagnosis and treatment” will provide the community with a comprehensive collection of information that represents the latest advances and concepts in this exciting field.

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