As unique molecules with both therapeutic and diagnostic properties, porphyrin derivatives have been extensively employed for cancer treatment. Porphyrins not only show powerful phototherapeutic effects (photodynamic and photothermal therapies), but also exhibit excellent imaging capacities, such as near-infrared fluorescent imaging (NIRFI), magnetic resonance imaging (MRI), photoacoustic imaging (PAI), positron emission tomography (PET), and single-photon emission computed tomography (SPECT). In order to take advantage of their robust phototherapeutic effects and excellent imaging capacities, porphyrins can be used to create nanomedicines with effective therapeutic and precise diagnostic properties for cancer treatment. In this Review, we summarize porphyrin-based nanomedicines which have been developed recently, including porphyrin-based liposomes, micelles, polymeric nanoparticles, peptide nanoparticles, and small-molecule nanoassemblies, and their applications on cancer therapy and diagnosis. The outlook and limitation of porphyrin-based nanomedicines are also reviewed.

Peptide-based materials hold great promise as immunotherapeutic agents for the treatment of many malignant cancers. Extensive studies have focused on the development of peptide-based cancer vaccines and delivery systems by mimicking the functional domains of proteins with highly specific immuno-regulatory functions or tumor cells fate controls. However, a systemic understanding of the interactions between the different peptides and immune systems remains unknown. This review describes the role of peptides in regulating the functions of the innate and adaptive immune systems and provides a comprehensive focus on the design, categories, and applications of peptide-based cancer vaccines. By elucidating the impacts of peptide length and formulations on their immunogenicity, peptide-based immunomodulating agents can be better utilized and dramatic breakthroughs may also be realized. Moreover, some critical challenges for translating peptides into large-scale synthesis, safe delivery, and efficient cancer immunotherapy are posed to improve the next-generation peptide-based immunotherapy.

Integration of the unique advantages of the fields of drug discovery and drug delivery is invaluable for the advancement of drug development. Here we propose a self-delivering one-component new-chemical-entity nanomedicine (ONN) strategy to improve cancer therapy through incorporation of the self-assembly principle into drug design. A lysosomotropic detergent (MSDH) and an autophagy inhibitor (Lys05) are hybridised to develop bisaminoquinoline derivatives that can intrinsically form nanoassemblies. The selected BAQ12 and BAQ13 ONNs are highly effective in inducing lysosomal disruption, lysosomal dysfunction and autophagy blockade and exhibit 30-fold higher antiproliferative activity than hydroxychloroquine used in clinical trials. These single-drug nanoparticles demonstrate excellent pharmacokinetic and toxicological profiles and dramatic antitumour efficacy in vivo. In addition, they are able to encapsulate and deliver additional drugs to tumour sites and are thus promising agents for autophagy inhibition-based combination therapy. Given their transdisciplinary advantages, these BAQ ONNs have enormous potential to improve cancer therapy.

Photodynamic therapy (PDT) has emerged as an attractive alternative in cancer therapy, but its therapeutic effects are limited by the nonselective subcellular localization and poor intratumoral retention of small‐molecule photosensitizes. Here a fiber‐forming nanophotosensitizer (PQC NF) that is composed of mitochondria targeting small molecules of amphiphilicity is reported. Harnessing the specific mitochondria targeting, the light‐activated PQC NFs produce approximately 110‐fold higher amount of reactive oxygen species in cells than free photosensitizers and can dramatically induce mitochondrial disruption to trigger intense apoptosis, showing 20–50 times better in vitro anticancer potency than traditional photosensitizers. As fiber‐shaped nanomaterials, PQC NFs also demonstrated a long‐term retention in tumor sites, solving the challenge of rapid clearance of small‐molecule photosensitizers from tumors. With these advantages, PQC NFs achieve a 100% complete cure rate in both subcutaneous and orthotopic oral cancer models with the administration of only a single dose. This type of single small molecule‐assembled mitochondria targeting nanofibers offers an advantageous strategy to improve the in vivo therapeutic effects of conventional PDT.

Real-time tracking of the dynamics change of self-assembled nanostructures in physiological environments is crucial to improving their delivery efficiency and therapeutic effects. However, such tracking is impeded by the complex biological microenvironment leading to inhomogeneous distribution. A rotatable fluorescent ratio strategy is introduced that integrates aggregation-induced emission (AIE) and aggregation-caused quenching (ACQ) into one nanostructured system, termed AIE and ACQ fluorescence ratio (AAR). Following this strategy, an advanced probe, PEG 5k -TPE 4 -ICGD 4 (PTI), is developed to track the dynamics change. The extremely sharp fluorescent changes (up to 4008-fold) in AAR allowed for the clear distinguishing and localization of the intact state and diverse dissociated states. The spatiotemporal distribution and structural dynamics of the PTI micelles can be tracked, quantitatively analyzed in living cells and animal tissue by the real-time ratio map, and be used to monitor other responsive nanoplatforms. With this method, the dynamics of nanoparticle in different organelles are able to be investigated and validated by transmission electron microscopy. This novel strategy is generally applicable to many self-assembled nanostructures for understanding delivery mechanism in living systems, ultimately to enhance their performance in biomedical applications.