In the long history of traditional Chinese medicine (TCM), meridians play essential roles as the critical network to regulate the normal physiological functions of the human body. They are regarded to be the channels connecting the internal organs with the body surface and various parts of the body. Although there are many studies and doctrines trying to reveal the nature of meridians for their validation in TCM, the mechanism underlying the meridians remains unclear. Herein, based on our macroscopic quantum state concept of ion channels (i.e., sub-nanometer scale channels), we propose a quantum principle of meridians. The acupoints and organ symptom are in a macroscopic coherence state of the ion channels in meridians. By applying TCM treatments (e.g., TCM massage, acupuncture, moxibustion, and electroacupuncture) on the acupoint, the corresponding organ symptom could be well regulated with help of quantum meridian state.

Intervaginal space injection (ISI) is a novel mode of administration investigated over the last decade. After injecting nanoparticles into the intervaginal space, they can be transported along low flow resistance channels into the interstitial space. This transport has a certain delivery direction, and site-specific injection can work on specific organs or tissues. In this study, the thorax, a new ISI site in the interstitial surrounding the internal thoracic artery named the thoracic interstitial injection (tISI) was investigated. To prove the targeting ability of the tISI, two sizes of gold nanoparticles (AuNPs) (47 and 87 nm) were administered to mice. After 1 h, the biodistribution of AuNPs in the tissues was measured via single particle inductively coupled plasma mass spectrometry (spICP-MS). The results showed that the concentration of AuNPs in the aorta after tISI injection was significantly higher than that after intravenous injection. Moreover, fewer nanoparticles with larger particle sizes were observed to have entered the blood and were better targeted to the aorta. Thereafter, tanshinone IIa sodium sulfonate liposomes were administered for the treatment of aortic atherosclerosis. The proportion of aortic plaques in atherosclerotic Apoe-/- mice administered via tISI was significantly lower than that in other model animals (P < 0.001). Furthermore, the proteoglycan content and CD68-positive cell count in the plaques were significantly reduced. The vascular elastic fibers at the plaque site were thickened, and fractures were reduced. tISI was, therefore, determined to be an effective strategy for the treatment of atherosclerotic aortic plaques.

The interstitial space, a widespread fluid-filled compartment throughout the body, is related to many pathophysiological alterations and diseases, attracting increasing attention. The vital role of interstitial space in malaria infection and treatment has been neglected current research efforts. We confirmed the reinfection capacity of parasites sequestrated in interstitial space, which replenish the mechanism of recurrence. Malaria parasite-infected mice were treated with artemisinin-loaded liposomes through the interstitial space and exhibited a better therapeutic response. Notably, compared with oral administration, interstitial administration showed an unexpectedly high activation and recruitment of immune cells, and resulted in better clearance of sequestered parasites from organs, and enhanced pathological recovery. The interstitial route of administration prolongs the blood circulation time of artemisinin and increases its plasma concentration, and may compensate for the inefficiency of oral administration and the nanotoxicity of intravenous administration, providing a potential strategy for infectious disease therapy.

Nowadays, nanoparticles (NPs) are considered to be ideal tools for bioimaging and drug delivery. Although increasing research has focused on NP biodistribution, transportation in the interstitial architecture has been neglected. The entire body is connected by the interstitial architecture, which can provide a long-range and direct pathway for NP biodistribution in a nonvascular system. In this study, we report that 10-nm gold NPs injected directly into the interstitial architecture of the tarsal tunnel of rats (intervaginal space injection (ISI)) were delivered to the brain without crossing the blood-brain barrier. Furthermore, NaGdF₄ nanoparticles were used to explore the transportation route by magnetic resonance imaging. The results demonstrated that, after ISI, the NaGdF₄ nanoparticles were transported through the perivascular interstitial space of the carotid arteries and brain vessels to the brain. This is a special nonvascular transportation route like a stream based on the interstitial architecture that provides an alternative pathway for NP biodistribution.

The fascia and the fascial space can help provide a better understanding of the body. An intervaginal space injection (ISI) provides unique advantages that require further investigation. An upper limb model including physiological conditions and the tumor process was chosen to determine the flow behavior of liquid metal after ISI. In normal rats, after the injection of liquid metal into the intervaginal space comprising tendons, vessels, and nerves, magnetic resonance imaging and an anatomy experiment indicated that the liquid metal wrapped around the fascial space and finally reached the fingertip downstream and the armpit upstream in addition to the neurovascular bundle without vessels or lymph nodes. Using environmental scanning electron microscopy (ESEM) images, we discovered that the liquid metal was wrapped around the fibers of the fascia and moved forward in microscale or nanoscale areas. These data confirmed a fascia-based pathway. In tumors, the liquid metal moved to the tumor capsule through the damaged spot, where cancer cells destroy the integrity of the fascia between the normal cells and cancer cells. The liquid metal partly wrapped around the tumor and separated the tumor from the surrounding normal muscle. The ESEM images showed that fibers of the fascia penetrated the tumor, thus forming a network through which the liquid metal penetrated the tumor. Our study illustrated the physiological and pathological flow behavior of liquid metal in the upper limb after ISI and demonstrated a nonvascular pathway in the fascia. ISI may be useful for clinical treatment in the fascial pathway.

The biodistribution of gold nanoparticles (AuNPs) is closely related to toxicological effects and is of great concern because of their potential application in diverse biomedical areas. However, with the discovery of novel anatomic and histological structures for fluid transport, the underlying mechanisms involved in the in vivo transport and biodistribution of AuNPs require further in-depth investigations. In the current study, we investigated the biodistribution of 10-nm AuNPs in rats after intervaginal space injection (ISI) in the tarsal tunnel, where a focal point of tendons, vessels, and nerve fibers may optimally connect to other remote connective tissues. The intravenous injection (IVI) of AuNPs served as a control. The blood and organs were collected at 5, 15, and 30 min and at 1, 4, 12, and 24 h after injection for quantitative analysis of Au distribution with inductively coupled plasma mass spectrometry (ICP-MS). IVI and ISI yielded significantly different results: The AuNP content in the blood after ISI was much lower than that after IVI; was similar in the lungs, heart, and intestines; and was higher in the skin and muscle. These findings were supported by the ratios of AuNP content and relative organ AuNP distribution proportions. Our results demonstrated a fast, direct, and the circulation-independent AuNP–organ transport pathway, which may improve our understanding of physiological and pathological biodistribution processes in biological systems. Furthermore, these results provide novel insights into the in vivo transport and biodistribution of AuNPs, which may lead to novel and efficient therapeutic and administration strategies.

Soft matter has attracted extensive attention due to its special physical/chemical properties and holds great promise in many applications. However, obtaining a detailed understanding of both complex fluid and mass transport in soft matter, especially in hierarchical porous media of biological tissues, still remains a huge challenge. Herein, inspired by fast tracer transport in loose connective tissues of living systems, we observed an interesting phenomenon of fast molecular transport in situ in an artificial hierarchical multiphase porous medium (a micrometer scale hydrophobic fiber network filled with nanometer scale hydrophilic porous medium), which was simply fabricated through electrospinning technology and polymerization. The transportation speed of molecules in the micrometer fiber network is larger than simple diffusion in nanometer media, which is better described by Fick's law. We further proved that the phenomenon is based on the nanoconfined air/water/solid interface around the micrometer hydrophobic fibers. We focus on the key factors, referring to S_A, (the confined multiphase area around the microfibers) and N_G (the connectivity node degree of the skeletal portion in the nanometer hydrogel medium). Next, a quantitative parameter, V_TCM (transport chance mean-value), was introduced to describe the molecular transport capability of the fiber network within hierarchical multiphase porous systems. These fundamental advances can be applied de novo to understand the process of so-called simple diffusion in biological systems, and even to re-describe many molecular events in biologically nanoconfined spaces.